1
|
Arecco L, Borea R, Magaton IM, Janković K, Mariamizde E, Stana M, Scavone G, Ottonello S, Spinaci S, Genova C, de Azambuja E, Lambertini M. Current practices in oncofertility counseling: updated evidence on fertility preservation and post-treatment pregnancies in young women affected by early breast cancer. Expert Rev Anticancer Ther 2024; 24:803-817. [PMID: 38913581 DOI: 10.1080/14737140.2024.2372337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 06/21/2024] [Indexed: 06/26/2024]
Abstract
INTRODUCTION Anticancer treatments have significantly contributed to increasing cure rates of breast cancer in the last years; however, they can also lead to short- and long-term side effects, including gonadotoxicity, and compromised fertility in young women. Oncofertility is a crucial issue for young patients who have not yet completed their family planning at the time of cancer diagnosis. AREAS COVERED This review aims to cover all the latest available evidence in the field of oncofertility, including the gonadotoxicity of currently adopted anticancer therapies in the curative breast cancer setting, the available strategies for fertility preservation and the feasibility of achieving a pregnancy following anticancer treatment completion. EXPERT OPINION Over the past years, a significant progress has been made in oncofertility care for young women with breast cancer. In the context of the currently available evidence, every young woman with newly diagnosed breast cancer should receive a proper and complete oncofertility counseling before starting any anticancer treatment to increase her chances of future pregnancies.
Collapse
Affiliation(s)
- Luca Arecco
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy
- Academic Trials Promoting Team, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium
| | - Roberto Borea
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Isotta Martha Magaton
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy
- Division of Gynaecological Endocrinology and Reproductive Medicine, University Women's Hospital, Bern, Switzerland
| | | | - Elene Mariamizde
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
- Department of Oncology and Hematology, Todua Clinic, Tbilisi, Georgia
| | - Mihaela Stana
- Department of Medical Oncology, Elysee Hospital, Alba Iulia, Romania
| | - Graziana Scavone
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Silvia Ottonello
- Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy
| | - Stefano Spinaci
- ASL3 Breast Unit Department, Division of Breast Surgery, Ospedale Villa Scassi, Genova, Italy
| | - Carlo Genova
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Evandro de Azambuja
- Academic Trials Promoting Team, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium
| | - Matteo Lambertini
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| |
Collapse
|
2
|
Nasri N, Saharkhiz S, Dini G, Yousefnia S. Thermo- and pH-responsive targeted lipid-coated mesoporous nano silica platform for dual delivery of paclitaxel and gemcitabine to overcome HER2-positive breast cancer. Int J Pharm 2023; 648:123606. [PMID: 37972671 DOI: 10.1016/j.ijpharm.2023.123606] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/09/2023] [Accepted: 11/11/2023] [Indexed: 11/19/2023]
Abstract
In the current study, a new monoclonal antibody conjugated dual stimuli lipid-coated mesoporous silica nanoparticles (L-MSNs) platform was developed and investigated for specific co-delivery of the paclitaxel (PTX) and gemcitabine (Gem) to cancer cells and preventing their side effects during the treatment process. First, MSNs were synthesized and then coated with as-prepared pH-, and thermo-sensitive niosomes to produce L-MSNs. For this aim, Dipalmitoylphosphatidylcholine (DPPC) was used to create thermo-sensitivity, and 1, 2-Distearoyl-sn-glycerol-3-phosphoethanolamine -Citraconic Anhydride-Polyethylene Glycol (DSPE-CA-PEG) polymers were prepared and incorporated to the lipid layer for creation of pH-sensitivity. In the next step, trastuzumab as a monoclonal antibody (mAb) was conjugated to the maleimide groups of the 1, 2-Distearoyl-sn-glycerol-3-phosphoethanolamine DSPE-polyethylene glycol (PEG)-maleimide agents in the lipid bilayer via a disulfide bond. Dynamic light scattering (DLS) and zeta potential measurements, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM) analyses were utilized to characterize the synthesized particles before and after surface modification. The encapsulation efficiency (EE%) and loading efficiency (LE%) of the particles were also evaluated. Additionally, the drug release study and MTT assay were done to evaluate the bioactivity potential of the fabricated platforms. The results of DLS and zeta potential measurements revealed an average size of 200 nm and a neutral zeta potential of about -1 mV for mAb-L-MSNs. Also, the FTIR spectra confirmed the formation of mAb-L-MSNs. Moreover, SEM analysis showed spherical-shaped MSNs with amorphous structure confirmed by XRD analysis, and BET test revealed ∼ 820 m2/g specific surface area and pore about 5 nm in size. The values of EE% and LE% of PTX were 90.3 % and 26.7 %, while these values for GEM were 89.5 % and 38.8 % in the co-loaded form, respectively. The thermo-pH-sensitivity examination showed approximately 500 nm of size increase after the change of pH and temperature from 7.4 and 37˚C to 5 and 42˚C. The release profile showed a pH-, and thermo-dependence manner, which led to about 89 % and 95 % of PTX and GEM released from the co-loaded platform at a pH of 5 and 42 °C while these values were 31.1 % and 32.2 % at pH of 7.4 and 37˚C, respectively. MTT assay data presented that when the mAb-L-co-loaded-MSNs platform containing 250 µg/mL drug was used, about 92 % of cells died in human epidermal receptors (HER2)-positive breast cancer cells (SKBR3), while just about 4 % of HER2-negative normal cells were killed. However, the growth inhibition rate of SKBR3 cells was caused by empty-mAb-L-MSNs, pure PTX and GEM combination were 9 % and 87 %, respectively. Moreover, the half inhibitory concentration (IC50) of the pure PTX, pure GEM, and mAb-coloaded-L-MSNs were 33, 17.6, and 6.5 µg/mL. The synergic effect of co-encapsulation of PTX and GEM in addition to trastuzumab conjugated L-MSNs was confirmed by a combinational index (CI) of 0.34. Therefore, this strategy leads to specific targeted drug delivery to cancer cells using a key-lock interaction between the trastuzumab and HER-2 receptors on the cancer cell membrane which stimuli the endocytosis of the particles to the cells followed by the destruction of the lipid layer in the acidic pH and the temperature of the lysosome, leading to enhanced release of PTX and GEM (pH of 5 and 42˚C). So, this platform can be considered a suitable carrier for cancer treatment.
Collapse
Affiliation(s)
- Negar Nasri
- Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 81746-73441, Iran
| | - Shaghayegh Saharkhiz
- Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 81746-73441, Iran
| | - Ghasem Dini
- Department of Nanotechnology, Faculty of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran.
| | - Saghar Yousefnia
- Department of Cell and Molecular Biology, Semnan University, Semnan, Iran
| |
Collapse
|
3
|
Loibl S, Azim HA, Bachelot T, Berveiller P, Bosch A, Cardonick E, Denkert C, Halaska MJ, Hoeltzenbein M, Johansson ALV, Maggen C, Markert UR, Peccatori F, Poortmans P, Saloustros E, Saura C, Schmid P, Stamatakis E, van den Heuvel-Eibrink M, van Gerwen M, Vandecaveye V, Pentheroudakis G, Curigliano G, Amant F. ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC). Ann Oncol 2023; 34:849-866. [PMID: 37572987 DOI: 10.1016/j.annonc.2023.08.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 07/31/2023] [Accepted: 08/01/2023] [Indexed: 08/14/2023] Open
Abstract
The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.
Collapse
Affiliation(s)
- S Loibl
- GBG c/o GBG Forschungs GmbH, Neu-Isenburg; Centre for Haematology and Oncology Bethanien, Frankfurt am Main, Frankfurt; Goethe University Frankfurt, Frankfurt am Main, Frankfurt, Germany.
| | - H A Azim
- Breast Cancer Center, School of Medicine, Tecnologico de Monterrey, San Pedro Garza Garcia, Nuevo Leon, Mexico
| | - T Bachelot
- Department of medical oncology, Centre Léon Bérard, Lyon, France
| | - P Berveiller
- Department of Gynecology and Obstetrics, Poissy-Saint Germain Hospital, Poissy; UMR 1198 - BREED, INRAE, Paris Saclay University, RHuMA, Montigny-Le-Bretonneux, France
| | - A Bosch
- Division of Oncology, Department of Clinical Sciences, Lund University, Lund; Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden
| | - E Cardonick
- Cooper Medical School at Rowan University, Camden, USA
| | - C Denkert
- Philipps-University Marburg and Marburg University Hospital (UKGM), Marburg, Germany
| | - M J Halaska
- Department of Obstetrics and Gynaecology, Third Faculty of Medicine, Charles University in Prague and Universital Hospital Kralovske Vinohrady, Prague, Czech Republic
| | - M Hoeltzenbein
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Clinical Pharmacology and Toxicology, Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy, Berlin, Germany
| | - A L V Johansson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Cancer Registry of Norway, Oslo, Norway
| | - C Maggen
- Department of Obstetrics and Prenatal Medicine, University Hospital Brussels, Brussels, Belgium
| | - U R Markert
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
| | - F Peccatori
- Gynecologic Oncology Department, European Institute of Oncology IRCCS, Milan, Italy
| | - P Poortmans
- Iridium Netwerk, Antwerp; University of Antwerp, Antwerp, Belgium
| | - E Saloustros
- Department of Oncology, University General Hospital of Larissa, Larissa, Greece
| | - C Saura
- Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - P Schmid
- Cancer Institute, Queen Mary University London, London, UK
| | - E Stamatakis
- Department of Anesthesiology, 'Alexandra' General Hospital, Athens, Greece
| | | | - M van Gerwen
- Gynecologic Oncology, Antoni van Leeuwenhoek-Netherlands Cancer Institute, Amsterdam; Department of Child and Adolescent Psychiatry and Psychosocial Care, Amsterdam UMC, University of Amsterdam; Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - V Vandecaveye
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - G Pentheroudakis
- European Society for Medical Oncology (ESMO), Lugano, Switzerland
| | - G Curigliano
- Division of Early Drug Development, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - F Amant
- Gynecologic Oncology, Antoni van Leeuwenhoek-Netherlands Cancer Institute, Amsterdam; Division Gynaecologic Oncology, UZ Leuven, Belgium
| |
Collapse
|
4
|
Zhu JW, Charkhchi P, Adekunte S, Akbari MR. What Is Known about Breast Cancer in Young Women? Cancers (Basel) 2023; 15:cancers15061917. [PMID: 36980802 PMCID: PMC10047861 DOI: 10.3390/cancers15061917] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/17/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
Breast cancer (BC) is the second leading cause of cancer-related death in women under the age of 40 years worldwide. In addition, the incidence of breast cancer in young women (BCYW) has been rising. Young women are not the focus of screening programs and BC in younger women tends to be diagnosed in more advanced stages. Such patients have worse clinical outcomes and treatment complications compared to older patients. BCYW has been associated with distinct tumour biology that confers a worse prognosis, including poor tumour differentiation, increased Ki-67 expression, and more hormone-receptor negative tumours compared to women >50 years of age. Pathogenic variants in cancer predisposition genes such as BRCA1/2 are more common in early-onset BC compared to late-onset BC. Despite all these differences, BCYW remains poorly understood with a gap in research regarding the risk factors, diagnosis, prognosis, and treatment. Age-specific clinical characteristics or outcomes data for young women are lacking, and most of the standard treatments used in this subpopulation currently are derived from older patients. More age-specific clinical data and treatment options are required. In this review, we discuss the epidemiology, clinicopathologic characteristics, outcomes, treatments, and special considerations of breast cancer in young women. We also underline future directions and highlight areas that require more attention in future studies.
Collapse
Affiliation(s)
- Jie Wei Zhu
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
- Department of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Parsa Charkhchi
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
| | - Shadia Adekunte
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
| | - Mohammad R Akbari
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
| |
Collapse
|
5
|
Bajpai J, Pathak R, Shylasree TS, Rugo HS. Management of breast cancer diagnosed during pregnancy: global perspectives. Expert Rev Anticancer Ther 2022; 22:1301-1308. [PMID: 36480337 DOI: 10.1080/14737140.2022.2150167] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Pregnancy-associated breast cancer (PABC) encompasses breast cancer diagnosed during pregnancy (BCP) or postpartum (PPBC). BCP is especially challenging with concerns regarding maternal and fetal safety synchronously. This review provides a comprehensive global view to optimize care of this unique entity. Areas covered Published literature and practices across the globe including real world published data from the first Indian registry are thoroughly reviewed to derive inferences. Diagnostic delays are common with resultant upstaging and inferior outcomes. Sonography-mammography and a biopsy with immunohistochemistry for estrogen, progesterone and HER-2neu receptors is mandatory. Multidisciplinary specialist teams are critical for trimester dependent management. Stage-wise surgical and systemic treatment remains largely similar to that of the nonpregnant women. Anthracyclines- and taxane-based chemotherapy is found to be safe after the 1st trimester. Frequent fetal and maternal monitoring is required to minimize complications. Chemotherapy should stop three weeks prior to the delivery to prevent peripartum infection/bleeding. Anti- Her-2 targeted therapy, endocrine therapy and radiation therapy are administered post-delivery. Iatrogenic premature delivery leads to poor neurocognition and should be avoided. Expert opinion Stage-wise outcomes are similar to that of non-pregnant patients with breast cancer, and underscores the importance of early detection especially in low- and middle-income countries. Global collaborations are warranted. AREAS COVERED Published literature and practices across the globe including real world published data from the first Indian registry are thoroughly reviewed to derive inferences. Diagnostic delays are common with resultant upstaging and inferior outcomes. Sonography-mammography and a biopsy with immunohistochemistry for estrogen, progesterone and HER-2neu receptors is mandatory. Multidisciplinary specialist teams are critical for trimester dependent management. Stage-wise surgical and systemic treatment remains largely similar to that of the nonpregnant women. Anthracyclines- and taxane-based chemotherapy is found to be safe after the 1st trimester. Frequent fetal and maternal monitoring is required to minimize complications. Chemotherapy should stop three weeks prior to the delivery to prevent peripartum infection/bleeding. Anti- Her-2 targeted therapy, endocrine therapy and radiation therapy are administered post-delivery. Iatrogenic premature delivery leads to poor neurocognition and should be avoided. EXPERT OPINION Stage-wise outcomes are similar to that of non-pregnant patients with breast cancer, and underscores the importance of early detection especially in low- and middle-income countries. Global collaborations are warranted.
Collapse
Affiliation(s)
- Jyoti Bajpai
- Department of Medical Oncology, Tata Memorial Centre, Mumbai, India
| | - Rima Pathak
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India
| | - T S Shylasree
- MD,FRCOG Consultant Gynaecological Oncologist, Aberdeen Royal Infirmary and NHS Grampian North Cancer Alliance United Kingdom, UK
| | - Hope S Rugo
- Professor of Medicine, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA
| |
Collapse
|
6
|
Update on Pregnancy Following Breast Cancer Diagnosis and Treatment. Cancer J 2022; 28:176-182. [PMID: 35594464 DOI: 10.1097/ppo.0000000000000599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ABSTRACT Survivorship has become a crucial component in breast cancer care. For women who have not completed their family planning, conceiving at the end of anticancer treatments should not be discouraged but might be challenging. Oncofertility counseling should be offered at the time of diagnosis to all patients, in order to inform them about the potential treatment-induced gonadotoxicity as well as the available strategies for fertility preservation, thus allowing to increase the chances of a future pregnancy. This article reports an updated overview on the current state of the art on pregnancy in women with prior breast cancer diagnosis and treatment, with a main focus on the issues faced by patients with history of hormone receptor-positive disease and BRCA carriers.
Collapse
|
7
|
Lambertini M, Blondeaux E, Bruzzone M, Perachino M, Anderson RA, de Azambuja E, Poorvu PD, Kim HJ, Villarreal-Garza C, Pistilli B, Vaz-Luis I, Saura C, Ruddy KJ, Franzoi MA, Sertoli C, Ceppi M, Azim HA, Amant F, Demeestere I, Del Mastro L, Partridge AH, Pagani O, Peccatori FA. Pregnancy After Breast Cancer: A Systematic Review and Meta-Analysis. J Clin Oncol 2021; 39:3293-3305. [PMID: 34197218 DOI: 10.1200/jco.21.00535] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/22/2021] [Accepted: 05/27/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics. METHODS A systematic literature review was conducted to identify studies including patients with a pregnancy after BC (PROSPERO number CRD42020158324). Likelihood of pregnancy after BC, their reproductive outcomes, and maternal safety were assessed. Pooled relative risks, odds ratios (ORs), and hazard ratios (HRs) with 95% CIs were calculated using random effects models. RESULTS Of 6,462 identified records, 39 were included involving 8,093,401 women from the general population and 112,840 patients with BC of whom 7,505 had a pregnancy after diagnosis. BC survivors were significantly less likely to have a subsequent pregnancy compared with the general population (relative risk, 0.40; 95% CI, 0.32 to 0.49). Risks of caesarean section (OR, 1.14; 95% CI, 1.04 to 1.25), low birth weight (OR, 1.50; 95% CI, 1.31 to 1.73), preterm birth (OR, 1.45; 95% CI, 1.11 to 1.88), and small for gestational age (OR, 1.16; 95% CI, 1.01 to 1.33) were significantly higher in BC survivors, particularly in those with previous chemotherapy exposure, compared with the general population. No significantly increased risk of congenital abnormalities or other reproductive complications were observed. Compared to patients with BC without subsequent pregnancy, those with a pregnancy had better disease-free survival (HR, 0.66; 95% CI, 0.49 to 0.89) and overall survival (HR, 0.56; 95% CI, 0.45 to 0.68). Similar results were observed after correcting for potential confounders and irrespective of patient, tumor, and treatment characteristics, pregnancy outcome, and timing of pregnancy. CONCLUSION These results provide reassuring evidence on the safety of conceiving in BC survivors. Patients' pregnancy desire should be considered a crucial component of their survivorship care plan.
Collapse
Affiliation(s)
- Matteo Lambertini
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy
- Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Eva Blondeaux
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy
- Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Marco Bruzzone
- Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Marta Perachino
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy
- Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Richard A Anderson
- MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom
| | - Evandro de Azambuja
- Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Philip D Poorvu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA
| | - Hee Jeong Kim
- Department of Surgical Oncology, Asan Medical Center, Seoul, Korea
| | - Cynthia Villarreal-Garza
- Breast Cancer Center, Hospital Zambrano Hellion, Tecnologico de Monterrey, San Pedro Garza Garcia, Nuevo Leon, Mexico
- Department of Breast Tumors, Instituo Nacional de Cancerologia, Mexico City, Mexico
| | - Barbara Pistilli
- Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Ines Vaz-Luis
- Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Cristina Saura
- Department of Medical Oncology, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | | | | | - Chiara Sertoli
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy
| | - Marcello Ceppi
- Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Hatem A Azim
- Breast Cancer Center, Hospital Zambrano Hellion, Tecnologico de Monterrey, San Pedro Garza Garcia, Nuevo Leon, Mexico
| | - Frederic Amant
- Netherlands Cancer Institute and Amsterdam University Medical Centers, Amsterdam, the Netherlands
- Department of Oncology, KU Leuven, Leuven, Belgium
| | - Isabelle Demeestere
- Fertility Clinic, CUB-Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Lucia Del Mastro
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy
- Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Ann H Partridge
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA
| | - Olivia Pagani
- Geneva University Hospitals, European School of Oncology, Geneva, Switzerland
| | - Fedro A Peccatori
- Fertility and Procreation Unit, Gynecologic Oncology Department, European Institute of Oncology IRCCS, Milan, Italy
| |
Collapse
|
8
|
Boudy AS, Grausz N, Selleret L, Gligorov J, Thomassin-Naggara I, Touboul C, Daraï E, Cadranel J. Use of tyrosine kinase inhibitors during pregnancy for oncogenic-driven advanced non-small cell lung carcinoma. Lung Cancer 2021; 161:68-75. [PMID: 34543940 DOI: 10.1016/j.lungcan.2021.09.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/22/2021] [Accepted: 09/06/2021] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Lung cancer associated with pregnancy is rare but on the increase. The use of tyrosine kinase inhibitor (TKI) therapy for advanced oncogenic-driven non-small cell lung carcinoma (NSCLC) has improved overall survival. Oncological and obstetric outcomes of patients diagnosed with NSCLC and treated by TKIs during pregnancy have been poorly evaluated. METHODS Three cases of NSCLC treated by TKIs during pregnancy were collected from the prospective database of the Cancer Associé à La Grossesse (CALG) network (France) in addition to eight cases identified by a systematic review performed between 2000 and 2021. RESULTS Among the eleven reported patients, six received an EGFR- and five an ALK-TKI. All patients were young nonsmokers and four had brain metastases at diagnosis. TKI treatment was initiated during the first trimester for three patients. Premature delivery was induced in 10/11 patients. Anamnios occurred in one patient treated by osimertinib and trastuzumab. Five newborns were hypotrophic. No newborn malformations were observed. Diffusion of the TKIs, confirmed by blood cord sampling, represented about 1/3 (EGFR-TKI) and 1/8 (ALK-TKI) of the maternal concentration. No developmental abnormalities were observed in the children (follow-up 30 months). The anti-tumor efficacy and tolerance of TKIs, when reported, appears similar to that described in the general population. CONCLUSIONS Our results support the rationale for using TKIs during pregnancy, both in terms of maternal NSCLC disease control and the relatively mild effects on the fetus. Our data will serve to better inform patients about the risks associated with TKIs used during pregnancy, contributing to shared decision making.
Collapse
Affiliation(s)
- Anne-Sophie Boudy
- Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France; Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France.
| | - Noémie Grausz
- Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France
| | - Lise Selleret
- Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France; Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France
| | - Joseph Gligorov
- Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France; APHP Tenon, INSERM U938, IUC-UPMC, Sorbonne University, Paris, France
| | - Isabelle Thomassin-Naggara
- Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France; APHP Tenon, INSERM U938, IUC-UPMC, Sorbonne University, Paris, France; Department of Radiology, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France
| | - Cyril Touboul
- Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France; Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France; APHP Tenon, INSERM U938, IUC-UPMC, Sorbonne University, Paris, France
| | - Emile Daraï
- Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France; Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France; APHP Tenon, INSERM U938, IUC-UPMC, Sorbonne University, Paris, France
| | - Jacques Cadranel
- Department of Pulmonology and Thoracic Oncology, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Tenon and GRC 04 Theranoscan, Sorbonne Université, Paris 75970, France.
| |
Collapse
|
9
|
Abstract
BACKGROUND Over than one third (28-58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. METHODS Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words "breast", "cancer", "trastuzumab" and "pregnancy". This study was performed in accordance with the PRISMA guidelines. RESULTS A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1-32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher's exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. CONCLUSIONS Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.
Collapse
|
10
|
Hu WK, Liu J, Liu RX, Liu XW, Yin CH. Congenital bilateral cryptorchidism in an infant conceived after maternal breast cancer treatment: A case report. World J Clin Cases 2021; 9:2923-2929. [PMID: 33969078 PMCID: PMC8058667 DOI: 10.12998/wjcc.v9.i12.2923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/26/2021] [Accepted: 02/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The incidence of breast cancer among women of reproductive age is increasing, as well as the desire for children at late childbearing age. Identifying factors that may be associated with fetal malformation and maternal and fetal prognosis has gained importance. We describe a 32-year-old woman with breast cancer who gave birth to a son with congenital bilateral cryptorchidism after treatment, with a literature review performed.
CASE SUMMARY A 32-year-old woman with breast cancer who had been treated by surgery and radiotherapy experienced recurrence and underwent a second surgery, adjuvant chemotherapy, and targeted therapy. Her tumor cells were negative for estrogen receptor (ER) α, progesterone receptor (PR), and p53; positive for ERβ, human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), and Ki67. She had pathogenic BRCA gene mutations. She became pregnant within 2 years and delivered a boy with congenital bilateral cryptorchidism. The boy underwent bilateral orchidopexy. As of this writing, the woman and her son are both healthy.
CONCLUSION HER2 overexpression, positivity for EGFR, Ki67, and ER, and PR negativity are associated with a poor prognosis in breast cancer. While no link has been established statistically between treatment for breast cancer and cryptorchidism in a subsequent pregnancy, this case suggests the possibility that ERβ and gene mutations may be contributing factors.
Collapse
Affiliation(s)
- Wei-Kai Hu
- Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Jing Liu
- Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Rui-Xia Liu
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Xiao-Wei Liu
- Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Cheng-Hong Yin
- Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| |
Collapse
|
11
|
Wolters V, Heimovaara J, Maggen C, Cardonick E, Boere I, Lenaerts L, Amant F. Management of pregnancy in women with cancer. Int J Gynecol Cancer 2021; 31:314-322. [PMID: 33649001 PMCID: PMC7925815 DOI: 10.1136/ijgc-2020-001776] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/25/2020] [Accepted: 09/28/2020] [Indexed: 01/04/2023] Open
Abstract
As the incidence of cancer in pregnancy has been increasing in recent decades, more specialists are confronted with a complex oncologic-obstetric decision-making process. With the establishment of (inter)national registries, including the International Network on Cancer, Infertility and Pregnancy, and an increasing number of smaller cohort studies, more evidence on the management of cancer during pregnancy is available. As fetal, neonatal, and short-term pediatric outcomes after cancer treatment are reassuring, more women receive treatment during pregnancy. Prenatal treatment should adhere to standard treatment as much as possible to optimize maternal prognosis, always taking into account fetal well-being. In order to guarantee the optimal treatment for both mother and child, a multidisciplinary team of specialists with expertise should be involved. Apart from oncologic treatment, a well-considered obstetric and perinatal management plan discussed with the future parents is crucial. Results of non-invasive prenatal testing are inconclusive in women with cancer and alternatives for prenatal anomaly screening should be used. Especially in women treated with chemotherapy, serial ultrasounds are strongly recommended to follow-up fetal growth and cervical length. After birth, a neonatal assessment allows the identification of any cancer or treatment-related adverse events. In addition, placental histologic examination aims to assess the fetal risk of metastasis, especially in women with malignant melanoma or metastatic disease. Breastfeeding is discouraged when systemic treatment needs to be continued after birth. At least a 3-week interval between the last treatment and nursing is recommended to prevent any treatment-induced neonatal effects from most non-platinum chemotherapeutic agents.
Collapse
Affiliation(s)
- Vera Wolters
- Department of Gynecology, Antoni van Leeuwenhoek Nederlands Kanker Instituut, Amsterdam, The Netherlands
| | | | - Charlotte Maggen
- Department of Obstetrics and Gynecology, University Hospitals Leuven and Department of Oncology, KU Leuven, Leuven, Belgium
| | - Elyce Cardonick
- Department of Obstetrics and Gynecology, Cooper University Health Care, Camden, New Jersey, USA
| | - Ingrid Boere
- Department of Medical Oncology, Erasmus MC Cancer Centre, Rotterdam, The Netherlands
| | | | - Frédéric Amant
- Department of Gynecology, Antoni van Leeuwenhoek Nederlands Kanker Instituut, Amsterdam, The Netherlands
- Department of Oncology, KU Leuven, Leuven, Belgium
| |
Collapse
|
12
|
Boudy AS, Ferrier C, Selleret L, Zilberman S, Arfi A, Sussfeld J, Gligorov J, Richard S, Bendifallah S, Chabbert-Buffet N, Touboul C, Daraï E. Prognosis of HER2-positive pregnancy-associated breast cancer: Analysis from the French CALG (Cancer Associé à La Grossesse) network. Breast 2020; 54:311-318. [PMID: 33271423 PMCID: PMC7711283 DOI: 10.1016/j.breast.2020.11.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/18/2020] [Accepted: 11/23/2020] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION The prevalence of pregnancy-associated breast cancer is increasing. HER2-positive breast cancers typically have a poor prognosis. The objective of our study was to compare the prognosis of patients with HER2-positive breast cancer diagnosed during pregnancy (HER2-positive BCP) to young women diagnosed with HER2-positive breast cancer outside of pregnancy (HER2 non-BCP). METHODS Data of patients managed for invasive breast carcinoma between January 2005 and 2020 were retrospectively collected from the database of Tenon University Hospital (Paris, France), part of the "Cancer lié à la Grossesse" network. RESULTS Fifty-one patients with HER2-positive BCP were matched on age at diagnosis with 51 HER2-positive non-BCP patients. Locally advanced disease with axillary lymph node involvement were frequent. Tumors were frequently aggressive with high grade (p = 0.57) and high Ki67 (p = 0.15). Among the HER2-positive BCP patients, the mean term at diagnosis was 19.3 week of gestation (WG). Eighty-four percent of the patients continued their pregnancy with a mean term at delivery of 34.2WG. Chemotherapy modalities differed between the two groups: neoadjuvant chemotherapy was more frequent in the HER2-positive BCP group (p = 0.03) and adjuvant chemotherapy more frequent in the HER2 non-BCP group (p = 0.009). The recurrence rate was 10% (n = 5) and 18% (n = 9) in the HER2-positive BCP and HER2 non-BCP groups, respectively, p = 0.25. Breast cancer-free survival was poorer in the HER2-positive BCP group with earlier recurrence, p = 0.008. No difference in type of recurrence was found between the groups (p = 0.58). CONCLUSION This matched case-control study implies that patients with HER2-positive BCP still have a poorer prognosis than non-pregnant HER-positive patients.
Collapse
Affiliation(s)
- Anne-Sophie Boudy
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France.
| | - Clément Ferrier
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France
| | - Lise Selleret
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France
| | - Sonia Zilberman
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France
| | - Alexandra Arfi
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France
| | - Julie Sussfeld
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France
| | - Joseph Gligorov
- Centre CALG (Cancer Associé à La Grossesse), France; Department of Oncology, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne Université, Institut Universitaire de Cancérologie (IUC), France; UMRS-938 4, Faculté de Médecine Sorbonne Université, France
| | - Sandrine Richard
- Centre CALG (Cancer Associé à La Grossesse), France; Department of Oncology, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne Université, Institut Universitaire de Cancérologie (IUC), France; UMRS-938 4, Faculté de Médecine Sorbonne Université, France
| | - Sofiane Bendifallah
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France; UMRS-938 4, Faculté de Médecine Sorbonne Université, France
| | - Nathalie Chabbert-Buffet
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France; UMRS-938 4, Faculté de Médecine Sorbonne Université, France
| | - Cyril Touboul
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France; UMRS-938 4, Faculté de Médecine Sorbonne Université, France
| | - Emile Daraï
- Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Sorbonne University, Institut Universitaire de Cancérologie (IUC), France; Centre CALG (Cancer Associé à La Grossesse), France; UMRS-938 4, Faculté de Médecine Sorbonne Université, France
| |
Collapse
|
13
|
Perachino M, Massarotti C, Razeti MG, Parisi F, Arecco L, Damassi A, Fregatti P, Solinas C, Lambertini M. Gender-specific aspects related to type of fertility preservation strategies and access to fertility care. ESMO Open 2020; 5:e000771. [PMID: 33115753 PMCID: PMC7594356 DOI: 10.1136/esmoopen-2020-000771] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/17/2020] [Accepted: 08/14/2020] [Indexed: 12/11/2022] Open
Abstract
Survivorship is an area of paramount importance to be addressed as early as possible after cancer diagnosis by all health care providers. On this regard, cancer care in young patients often poses several age-related considerations among which fertility and pregnancy-related issues have a crucial role. According to the available guidelines on the topic, all patients with cancer diagnosed during their reproductive years should be provided a proper oncofertility counselling before starting anticancer treatments. This is an important step in order to inform patients about the potential treatment-induced gonadotoxicity and the available strategies for fertility preservation so that they can be referred as early as possible to fertility specialists if potentially interested in these options.In this manuscript, we aim to provide an up to date overview on the available efficacy and safety data with the main strategies for fertility preservation in male and female cancer patients in order to help optimising the oncofertility counselling performed by healthcare providers involved in cancer care and dealing with young patients. In male patients with cancer, sperm cryopreservation is the standard technique for fertility preservation. Oocyte/embryo cryopreservation, ovarian tissue cryopreservation and temporary ovarian suppression with luteinising hormone-releasing hormone agonists during chemotherapy are the main options in female patients with cancer.A multidisciplinary management building a strong network between fertility and oncology/haematology units is crucial to properly address fertility care in all young patients with cancer, at both diagnosis and during oncologic follow-up. Discussing fertility and pregnancy-related issues with young patients with cancer has to be considered mandatory nowadays keeping in mind that returning to a normal life (including the possibility to have a family and to live with as few side effects as possible) should be considered an important ambition in cancer care in the 21st century .
Collapse
Affiliation(s)
- Marta Perachino
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Liguria, Italy; Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Claudia Massarotti
- Physiopatology of Human Reproduction Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Maria Grazia Razeti
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Liguria, Italy; Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Francesca Parisi
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Liguria, Italy; Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Luca Arecco
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Liguria, Italy; Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Alessandra Damassi
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Liguria, Italy; Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Piero Fregatti
- Department of Surgery, U.O.C. Clinica di Chirurgia Senologica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Integrated Diagnostic Surgical Sciences, School of Medicine, University of Genova, Genova, Italy
| | - Cinzia Solinas
- Medical Oncology, Azienda Tutela della Salute Sardegna, Hospital A. Segni Ozieri, Sassari, Italy
| | - Matteo Lambertini
- Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Liguria, Italy; Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
| |
Collapse
|
14
|
Berwart J, Buonomo B, Peccatori FA, Marioni A, Lescano J, Pressel Coretto E. Management of HER2-positive breast cancer during pregnancy: a case report. TUMORI JOURNAL 2020; 106:NP33-NP35. [PMID: 32729389 DOI: 10.1177/0300891620944218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Breast cancer is one of the most common malignancies diagnosed during pregnancy, with an incidence of 1:3000 pregnancies. Its rising incidence is related to the trend to postpone childbearing during the last 30 years. Breast cancer during pregnancy should not be managed differently from the nonpregnant setting. Chemotherapy is reported to be safe after the first trimester, whereas trastuzumab and tamoxifen are contraindicated regardless of the trimester. CASE DESCRIPTION A patient diagnosed with breast cancer recurrence during pregnancy was exposed to both tamoxifen and trastuzumab during the first two trimesters of pregnancy. In addition, docetaxel was administered during the second and third trimesters, without subsequent fetal malformations or obstetric complications. CONCLUSIONS When conception occurs inadvertently during assumption of tamoxifen or anti-HER2 agents, their effects on the fetus and on the course of pregnancy are not completely understood. Further studies are needed in this setting, highlighting the importance to share clinical experiences.
Collapse
Affiliation(s)
- Julia Berwart
- Department of Gynecology, Justo José de Urquiza Hospital, Concepción del Uruguay, Entre Ríos, Argentina
| | - Barbara Buonomo
- Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology IRCCS, Milan, Italy
| | - Fedro A Peccatori
- Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology IRCCS, Milan, Italy
| | - Anabel Marioni
- Department of Gynecology, Justo José de Urquiza Hospital, Concepción del Uruguay, Entre Ríos, Argentina
| | - Juliana Lescano
- Department of Gynecology, Justo José de Urquiza Hospital, Concepción del Uruguay, Entre Ríos, Argentina
| | - Emilia Pressel Coretto
- Department of Gynecology, Justo José de Urquiza Hospital, Concepción del Uruguay, Entre Ríos, Argentina
| |
Collapse
|
15
|
Maggen C, Lok CA, Cardonick E, van Gerwen M, Ottevanger PB, Boere IA, Koskas M, Halaska MJ, Fruscio R, Gziri MM, Witteveen PO, Van Calsteren K, Amant F. Gastric cancer during pregnancy: A report on 13 cases and review of the literature with focus on chemotherapy during pregnancy. Acta Obstet Gynecol Scand 2019; 99:79-88. [PMID: 31529466 PMCID: PMC6972614 DOI: 10.1111/aogs.13731] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 09/05/2019] [Accepted: 09/11/2019] [Indexed: 12/14/2022]
Abstract
Introduction Gastric cancer during pregnancy is extremely rare and data on optimal treatment and possible chemotherapeutic regimens are scarce. The aim of this study is to describe the obstetric and maternal outcome of women with gastric cancer during pregnancy and review the literature on antenatal chemotherapy for gastric cancer. Material and methods Treatment and outcome of patients registered in the International Network on Cancer, Infertility and Pregnancy database with gastric cancer diagnosed during pregnancy were analyzed. Results In total, 13 women with gastric cancer during pregnancy were registered between 2002 and 2018. Median gestational age at diagnosis was 22 weeks (range 6‐30 weeks). Twelve women were diagnosed with advanced disease and died within 2 years after pregnancy, most within 6 months. In total, eight out of 10 live births ended in a preterm delivery because of preeclampsia, maternal deterioration, or therapy planning. Two out of six women who initiated chemotherapy during pregnancy delivered at term. Two neonates prenatally exposed to chemotherapy were growth restricted and one of them developed a systemic infection with brain abscess after preterm delivery for preeclampsia 2 weeks after chemotherapy. No malformations were reported. Conclusions The prognosis of gastric cancer during pregnancy is poor, mainly due to advanced disease at diagnosis, emphasizing the need for early diagnosis. Antenatal chemotherapy can be considered to reach fetal maturity, taking possible complications such as growth restriction, preterm delivery, and hematopoietic suppression at birth into account.
Collapse
Affiliation(s)
- Charlotte Maggen
- Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium.,Department of Oncology, KU Leuven, Leuven, Belgium
| | - Christianne A Lok
- Center for Gynecological Oncology Amsterdam, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Elyce Cardonick
- Department of Obstetrics and Gynecology, Cooper, University Health Care, Camden, NJ, USA
| | - Mathilde van Gerwen
- Center for Gynecological Oncology Amsterdam, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Amsterdam, The Netherlands.,Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Petronella B Ottevanger
- Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
| | - Ingrid A Boere
- Department of Medical Oncology, Erasmus MC Cancer, Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Martin Koskas
- Gynecologic Oncology, Bichat University Hospital, Paris Diderot University, Paris, France
| | - Michael J Halaska
- Faculty Hospital Kralovske, Vinohrady and 3rd Medical Faculty, Charles University, Prague, Czech Republic
| | - Robert Fruscio
- Clinic of Obstetrics and Gynecology, University of Milan - Bicocca, San Gerardo Hospital, Monza, Italy
| | - Mina M Gziri
- Department of Obstetrics, Cliniques Universitaires St Luc, UCL, Sint-Lambrechts-Woluwe, Belgium
| | - Petronella O Witteveen
- Department of Medical Oncology, Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Kristel Van Calsteren
- Department of Obstetrics, University Hospitals Leuven, Leuven and Department of Development and regeneration, KU Leuven, Leuven, Belgium
| | - Frédéric Amant
- Department of Oncology, KU Leuven, Leuven, Belgium.,Center for Gynecological Oncology Amsterdam, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Amsterdam, The Netherlands.,Center for Gynecological Oncology Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | | |
Collapse
|
16
|
Abstract
Trastuzumab and pertuzumab are monoclonal antibodies used for the treatment of breast cancer. Until now, there have been no reports on the use of pertuzumab during pregnancy and on its potential effects on the fetus. Herein, we present a breast cancer patient who received trastuzumab and pertuzumab treatment during the first 20 weeks of pregnancy. This 22-year-old patient initially diagnosed with invasive ductal carcinoma of the breast was found to be negative for estrogen receptor and progesterone receptor and positive for human epidermal growth factor receptor in the immunohistochemical examination. At the time of diagnosis, she had metastatic lesions and a protocol of docetaxel, trastuzumab, pertuzumab, q21, and zolendronic acid 4 mg every month was started. Following six courses of therapy, she had near-complete response, and, after administration of the same course of treatment for two additional cycles, treatment with pertuzumab plus trastuzumab was continued. While she was being followed-up with remission, a 20-week pregnancy was detected. A fetal ultrasound examination showed oligohydramnios and right renal agenesis. Treatment was stopped, and the fetus was monitored. After 7 weeks of follow-up, fetal growth retardation and anhydramnios were detected. The pregnancy was terminated. Fetal autopsy showed no urinary system pathology, but macroscopic and microscopic hyperplasia of the right adrenal gland was identified. Concomitant use of pertuzumab and trastuzumab during pregnancy may be associated with an unresolved oligohydramnios and/or anhydramnios risk. Extreme caution should be used when these monoclonal antibodies are administered during pregnancy.
Collapse
|
17
|
Goller SS, Markert UR, Fröhlich K. Trastuzumab in the Treatment of Pregnant Breast Cancer Patients - an Overview of the Literature. Geburtshilfe Frauenheilkd 2019; 79:618-625. [PMID: 31217630 PMCID: PMC6570610 DOI: 10.1055/a-0880-9295] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 02/08/2019] [Accepted: 03/20/2019] [Indexed: 01/11/2023] Open
Abstract
Breast cancer is one of the most common malignancies which appear during pregnancy. Since women are increasingly not giving birth until they are at a more advanced age, it can be assumed that the incidence of pregnancy-related breast cancers will continue to increase in the future. Because of pregnancy-induced changes and conservative diagnosis, these carcinomas are frequently not detected until they are at an advanced stage and thus generally require systemic adjuvant therapy. The available data on optimal chemotherapeutic management are limited. Particularly for the use of the target agent trastuzumab which could crucially contribute to improving the prognosis in the therapy of HER2-overexpressing breast cancer in non-pregnant women, there is a lack of definitive information regarding the profile of action and safety in pregnancy as well as with regard to any long-term effects on the child. Thirty-eight pregnancies on trastuzumab for the treatment of breast cancer were able to be analysed in the literature currently available. Information can be gained from this and conclusions can be drawn which can individualise and decisively improve therapeutic options in the future for the pregnant breast cancer patient.
Collapse
Affiliation(s)
- Sophia S Goller
- Universitätsklinikum Jena, Klinik für Geburtsmedizin, Placenta-Labor, Jena, Germany
| | - Udo R Markert
- Universitätsklinikum Jena, Klinik für Geburtsmedizin, Placenta-Labor, Jena, Germany
| | - Karolin Fröhlich
- Universitätsklinikum Jena, Klinik für Geburtsmedizin, Placenta-Labor, Jena, Germany
| |
Collapse
|
18
|
Lambertini M, Viglietti G. Pregnancies in young women with diagnosis and treatment of HER2-positive breast cancer. Oncotarget 2019; 10:803-804. [PMID: 30783509 PMCID: PMC6368228 DOI: 10.18632/oncotarget.26611] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 01/14/2019] [Indexed: 11/25/2022] Open
Affiliation(s)
- Matteo Lambertini
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, Genova, Italy
| | - Giulia Viglietti
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, Genova, Italy
| |
Collapse
|
19
|
Lambertini M, Martel S, Campbell C, Guillaume S, Hilbers FS, Schuehly U, Korde L, Azim HA, Di Cosimo S, Tenglin RC, Huober J, Baselga J, Moreno-Aspitia A, Piccart-Gebhart M, Gelber RD, de Azambuja E, Ignatiadis M. Pregnancies during and after trastuzumab and/or lapatinib in patients with human epidermal growth factor receptor 2-positive early breast cancer: Analysis from the NeoALTTO (BIG 1-06) and ALTTO (BIG 2-06) trials. Cancer 2018; 125:307-316. [PMID: 30335191 DOI: 10.1002/cncr.31784] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 06/08/2018] [Accepted: 06/14/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND Limited data exist on the safety of using anti-human epidermal growth factor receptor 2 (HER2) targeted agents during pregnancy. To date, only retrospective studies have assessed the prognosis of patients with a pregnancy after prior early breast cancer, with no data in HER2-positive patients. METHODS The Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial and the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial were randomized phase 3 trials for patients with HER2-positive early breast cancer. In both trials, pregnancy information was prospectively collected. Pregnancy outcomes were compared between patients unintentionally exposed to trastuzumab and/or lapatinib during gestation (the exposed group) and those who became pregnant after trastuzumab and/or lapatinib completion (the unexposed group). In the ALTTO trial, disease-free survival (DFS) was compared between pregnant patients and those aged 40 years or younger without a subsequent pregnancy via an extended Cox model with time-varying covariates to account for a guarantee-time bias. RESULTS Ninety-two patients (12 in the exposed group and 80 in the unexposed group) had a pregnancy: 7 in the NeoALTTO trial and 85 in the ALTTO trial. Seven patients (58.3%) in the exposed group and 10 patients (12.5%) in the unexposed group opted for an induced abortion; in the unexposed group, 10 patients (12.5%) had a spontaneous abortion. No pregnancy/delivery complications were reported for the remaining cases, who successfully completed their pregnancy, with the exception of 1 fetus with trisomy 21 (Down syndrome). No significant difference in DFS (adjusted hazard ratio, 1.12; 95% confidence interval, 0.52-2.42) was observed between young patients with a pregnancy (n = 85) and young patients without a pregnancy (n = 1307). CONCLUSIONS For patients with HER2-positive early breast cancer, having a pregnancy after treatment completion appears to be safe without compromising fetal outcome or maternal prognosis.
Collapse
Affiliation(s)
- Matteo Lambertini
- Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Samuel Martel
- Department of Hemato-Oncology, CISSS Montérégie-Centre/Hôpital Charles-Le Moyne, Université de Sherbrooke, Quebec, Canada
| | | | - Sébastien Guillaume
- Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
| | | | | | | | - Hatem A Azim
- Department of Medicine, Division of Hematology/Oncology, American University of Beirut, Beirut, Lebanon
| | | | | | - Jens Huober
- Breast Center, University of Ulm, Ulm, Germany
| | - José Baselga
- Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Martine Piccart-Gebhart
- Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Richard D Gelber
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.,Harvard TH Chan School of Public Health, Boston, Massachusetts.,Frontier Science and Technology Research Foundation, Boston, Massachusetts
| | - Evandro de Azambuja
- Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Michail Ignatiadis
- Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
| |
Collapse
|
20
|
Wan C, Arès I, Gareau A, Collins KA, Lebel S, Bielajew C. Motherhood and well-being in young breast cancer survivors. BREAST CANCER MANAGEMENT 2018. [DOI: 10.2217/bmt-2017-0015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: This exploratory study aimed to examine differences in well-being between young breast cancer survivors (BCS) with and without children. Materials & methods: Participants (n = 816) completed an online survey relating to quality of life, illness intrusiveness, fear of cancer recurrence, stress and social support. Results: Exploratory and confirmatory factor analyses revealed similar models of well-being between both groups, but with a stronger relationship between psychological adjustment and illness intrusiveness for BCS with children (r = -0.779, 95% CI: -0.711, -0.848 vs r = -0.525, 95% CI: -0.423, -0.627). Conclusion: Parenting compromises the overall well-being of young BCS with children and they would therefore benefit from interventions and social and oncological support programs, especially for those caring for minor children.
Collapse
Affiliation(s)
- Cynthia Wan
- School of Psychology, University of Ottawa, 136 Jean Jacques Lussier Pvt, Ottawa, ON K1N 6N5, Canada
| | - Isabelle Arès
- The Royal Ottawa Mental Health Centre, 1145 Carling Ave, Ottawa, ON K1Z 7K4, Canada
| | - Alexandre Gareau
- School of Psychology, University of Ottawa, 136 Jean Jacques Lussier Pvt, Ottawa, ON K1N 6N5, Canada
| | - Katherine A Collins
- Department of Psychology, Concordia University of Edmonton, 7128 Ada Blvd NW, Edmonton, AB T5B 4E4, Canada
| | - Sophie Lebel
- School of Psychology, University of Ottawa, 136 Jean Jacques Lussier Pvt, Ottawa, ON K1N 6N5, Canada
| | - Catherine Bielajew
- School of Psychology, University of Ottawa, 136 Jean Jacques Lussier Pvt, Ottawa, ON K1N 6N5, Canada
| |
Collapse
|
21
|
Peccatori FA, Lambertini M, Scarfone G, Del Pup L, Codacci-Pisanelli G. Biology, staging, and treatment of breast cancer during pregnancy: reassessing the evidences. Cancer Biol Med 2018; 15:6-13. [PMID: 29545964 PMCID: PMC5842335 DOI: 10.20892/j.issn.2095-3941.2017.0146] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy (BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.
Collapse
Affiliation(s)
| | - Matteo Lambertini
- Gynecologic Oncology Department, European Institute of Oncology, Milan 20141, Italy
| | - Giovanna Scarfone
- Gynecologic Oncology Department, European Institute of Oncology, Milan 20141, Italy
| | - Lino Del Pup
- Gynecologic Oncology Department, European Institute of Oncology, Milan 20141, Italy
| | | |
Collapse
|
22
|
Abstract
PURPOSE OF REVIEW Cancer in pregnancy has become increasingly frequent. It has become clear that for specific cancers under well defined circumstances, oncological treatment in pregnancy can be well tolerated and feasible for both mother and fetus. Continued critical assessment of the available literature and registration of cancer in pregnancy cases and outcomes for mother and child are necessary to work toward implementing optimal cancer treatment during pregnancy. RECENT FINDINGS Physiologic changes in pregnancy may alter distribution and efficacy of systemic therapy. Data on systemic therapy including, chemotherapy, hormonal therapy, and targeted therapy during pregnancy are available but incomplete. Outcomes of fetuses exposed to chemotherapy in utero are generally reassuring, but new targeted therapies are mostly discouraged in pregnancy. SUMMARY Cancer treatment during pregnancy is possible, depending on type and timing of systemic therapy and treatment modality. Available data are reassuring with a modest increase in complications such as growth restriction and preterm birth. The effect of new targeted therapies is often still unclear and therefore discouraged.
Collapse
|
23
|
Knabben L, Mueller MD. Breast cancer and pregnancy. Horm Mol Biol Clin Investig 2017; 32:/j/hmbci.ahead-of-print/hmbci-2017-0026/hmbci-2017-0026.xml. [PMID: 28850544 DOI: 10.1515/hmbci-2017-0026] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 07/17/2017] [Indexed: 11/15/2022]
Abstract
Background In the past decades the incidence of pregnancy-associated breast cancer (PABC) increased. Possible explanations are the trend to postpone childbearing and the general increase in the incidence of breast cancer. Materials and methods A sytematic review of the literature was performed with the aim to report on incidence, diagnosis, treatment and prognosis of breast cancer during pregnancy. We also cover the issue of pregnancy following a diagnosis of breast cancer including fertility preservation and prognosis. Results Ultrasound is the imaging method of choice in pregnancy, but mammography can also be performed as the fetal irradiation dose is low. To avoid a delay in diagnosis every sonographic mass in pregnant women which does not clearly correspond to a cyst needs further investigation by biopsy. Treatment should follow as close as possible the guidelines for non-pregnant patients. Administration of chemotherapy is possible after the first trimester. There is a large body of evidence for the use of anthracyclines. In contrast radiotherapy, trastuzumab and antihormonal treatment by tamoxifen are contraindicated during pregnancy. Pregnancy does not seem to influence prognosis. Most adverse obstetric outcomes are related to preterm delivery, which should therefore, whenever possible, be avoided. Young patients with breast cancer and incomplete family planning should be referred for counseling about fertility preservation options before the initiation of adjuvant treatment. A pregnancy following breast cancer does not have a negative impact on prognosis. Conclusion Multidisciplinary management of women with breast cancer in pregnancy is mandatory and data should be collected to allow further improvement in management.
Collapse
Affiliation(s)
- Laura Knabben
- Department of Obstetrics and Gynaecology, University Hospital of Berne, Effingerstrasse 102, 3010 Berne, Switzerland, Phone: +41 31 632 10 10, Fax: +41 31 632 12 05
| | - Michel D Mueller
- Department of Obstetrics and Gynaecology, University Hospital of Berne and University of Berne, Berne, Switzerland
| |
Collapse
|
24
|
Lorenzi E, Simonelli M, Santoro A. Infertility risk and teratogenicity of molecularly targeted anticancer therapy: A challenging issue. Crit Rev Oncol Hematol 2016; 107:1-13. [PMID: 27823636 DOI: 10.1016/j.critrevonc.2016.08.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 06/20/2016] [Accepted: 08/16/2016] [Indexed: 01/06/2023] Open
Abstract
The growing population of young cancer survivors and a trend toward postponing pregnancy until later in life are shifting areas of focus toward understanding treatment induced sequelae, particularly the effects of cancer and/or treatment on fertility. Whereas the fertility risk of cytotoxic agents for both men and women is well-recognized, the fertility risks and teratogenic potential associated with molecular targeted therapies are not established. We summarize available preclinical and clinical data on the impact of new molecular targeted agents on fertility in both sexes, and their potential teratogenic effects, providing recommendations for clinicians, where possible. Agents were categorized by class and the potential relevance of their target signaling pathways to gonadal maturation discussed.
Collapse
Affiliation(s)
- Elena Lorenzi
- Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy.
| | - Matteo Simonelli
- Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy
| | - Armando Santoro
- Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy; Humanitas University, Rozzano Milan, Italy
| |
Collapse
|
25
|
Miyamoto S, Yamada M, Kasai Y, Miyauchi A, Andoh K. Anticancer drugs during pregnancy. Jpn J Clin Oncol 2016; 46:795-804. [PMID: 27284093 DOI: 10.1093/jjco/hyw073] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 05/17/2016] [Indexed: 11/12/2022] Open
Abstract
Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs.
Collapse
Affiliation(s)
- Shingo Miyamoto
- Department of Medical Oncology, Japanese Red Cross Medical Center, Shibuya, Tokyo
| | - Manabu Yamada
- Department of Gynecology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan
| | - Yasuyo Kasai
- Department of Gynecology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan
| | - Akito Miyauchi
- Department of Gynecology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan
| | - Kazumichi Andoh
- Department of Gynecology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan
| |
Collapse
|
26
|
Zagouri F, Dimitrakakis C, Marinopoulos S, Tsigginou A, Dimopoulos MA. Cancer in pregnancy: disentangling treatment modalities. ESMO Open 2016; 1:e000016. [PMID: 27843602 PMCID: PMC5070264 DOI: 10.1136/esmoopen-2015-000016] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 03/29/2016] [Accepted: 03/30/2016] [Indexed: 01/25/2023] Open
Abstract
Pregnancy-associated cancer constitutes an uncommon and difficult to manage clinical situation. It is defined as the cancer diagnosed from the first day of childbearing to 1 year post partum. Coexistence of cancer with pregnancy adds complexity to treatment recommendations, as both the mother and the fetus may be affected. The optimal therapeutic management of pregnant women with cancer diagnosis should take into account, apart from medical factors, a host of other parameters (ethical, psychological, religious, legal, etc). Unfortunately, this situation becomes more complex as more women delay childbearing, and consequently the incidence of cancer during pregnancy is constantly increasing. This manuscript summarises the general principles in managing pregnant patients with cancer and gives detailed instructions in the management of pregnant patients with breast cancer, ovarian cancer, melanoma, lymphoma, lung cancer, soft-tissue sarcoma and cervical cancer. Of note, management of pregnant women with cancer diagnosis should be performed in specialised centres with experience and all cases should be discussed in multidisciplinary meetings composed of multiple specialists (medical oncologists, obstetricians, surgeons, radiologists and paediatricians).
Collapse
Affiliation(s)
- Flora Zagouri
- Department of Clinical Therapeutics , Alexandra Hospital, National and Kapodistrian University of Athens, School of Medicine , Athens , Greece
| | - Constantine Dimitrakakis
- Department of Obstetrics and Gynecology , Alexandra Hospital, National and Kapodistrian University of Athens, School of Medicine , Athens , Greece
| | - Spyridon Marinopoulos
- Department of Obstetrics and Gynecology , Alexandra Hospital, National and Kapodistrian University of Athens, School of Medicine , Athens , Greece
| | - Alexandra Tsigginou
- Department of Obstetrics and Gynecology , Alexandra Hospital, National and Kapodistrian University of Athens, School of Medicine , Athens , Greece
| | - Meletios-Athanassios Dimopoulos
- Department of Clinical Therapeutics , Alexandra Hospital, National and Kapodistrian University of Athens, School of Medicine , Athens , Greece
| |
Collapse
|
27
|
|
28
|
Current challenges in HER2-positive breast cancer. Crit Rev Oncol Hematol 2016; 98:211-21. [DOI: 10.1016/j.critrevonc.2015.10.016] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2015] [Revised: 10/06/2015] [Accepted: 10/28/2015] [Indexed: 12/13/2022] Open
|
29
|
Lambertini M, Del Mastro L, Pescio MC, Andersen CY, Azim HA, Peccatori FA, Costa M, Revelli A, Salvagno F, Gennari A, Ubaldi FM, La Sala GB, De Stefano C, Wallace WH, Partridge AH, Anserini P. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med 2016; 14:1. [PMID: 26728489 PMCID: PMC4700580 DOI: 10.1186/s12916-015-0545-7] [Citation(s) in RCA: 353] [Impact Index Per Article: 39.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 12/16/2015] [Indexed: 12/28/2022] Open
Abstract
In the last years, thanks to the improvement in the prognosis of cancer patients, a growing attention has been given to the fertility issues. International guidelines on fertility preservation in cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed fertility preservation decisions. As recommended by the American Society of Clinical Oncology and the European Society for Medical Oncology, sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservations in male and female patients, respectively; other strategies (e.g. pharmacological protection of the gonads and gonadal tissue cryopreservation) are considered experimental techniques. However, since then, new data have become available, and several issues in this field are still controversial and should be addressed by both patients and their treating physicians.In April 2015, physicians with expertise in the field of fertility preservation in cancer patients from several European countries were invited in Genova (Italy) to participate in a workshop on the topic of "cancer and fertility preservation". A total of ten controversial issues were discussed at the conference. Experts were asked to present an up-to-date review of the literature published on these topics and the presentation of own unpublished data was encouraged. On the basis of the data presented, as well as the expertise of the invited speakers, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation.Although there is a great interest in this field, due to the lack of large prospective cohort studies and randomized trials on these topics, the level of evidence is not higher than 3 for most of the recommendations highlighting the need of further research efforts in many areas of this field. The participation to the ongoing registries and prospective studies is crucial to acquire more robust information in order to provide evidence-based recommendations.
Collapse
Affiliation(s)
- Matteo Lambertini
- Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Genoa, Italy.
| | - Lucia Del Mastro
- Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Genoa, Italy
| | - Maria C Pescio
- Physiopathology of Human Reproduction, IRCCS AOU San Martino - IST, Genoa, Italy
| | - Claus Y Andersen
- Laboratory of Reproductive Biology, Section 5712, Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, Copenhagen, Denmark
| | - Hatem A Azim
- BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Fedro A Peccatori
- Fertility and Procreation Unit, Gynecologic Oncology Department, European Institute of Oncology, Milan, Italy
| | - Mauro Costa
- Reproductive Medicine Department, International Evangelic Hospital, Genoa, Italy
| | - Alberto Revelli
- Physiopathology of Reproduction and In Vitro Fertilization Unit, S. Anna Hospital, University of Turin, Turin, Italy
| | - Francesca Salvagno
- Physiopathology of Reproduction and In Vitro Fertilization Unit, S. Anna Hospital, University of Turin, Turin, Italy
| | | | - Filippo M Ubaldi
- GENERA Centre for Reproductive Medicine, Clinica Valle Giulia, Rome, Italy
| | - Giovanni B La Sala
- Obstetric and Gynecology Department, Azienda Ospedaliera Arcispedale S. Maria Nuova-IRCCS, University of Modena and Reggio Emilia, Reggio Emilia, Italy
| | - Cristofaro De Stefano
- Children and Women Health Department, Physiopathology of Human Reproduction Unit, "San Giuseppe Moscati" Hospital, Avellino, Italy
| | - W Hamish Wallace
- Department of Haematology/Oncology, Royal Hospital for Sick Children, and Department of Child Life and Health, University of Edinburgh, Edinburgh, UK
| | - Ann H Partridge
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Paola Anserini
- Physiopathology of Human Reproduction, IRCCS AOU San Martino - IST, Genoa, Italy
| |
Collapse
|
30
|
Ademuyiwa FO, Cyr A, Ivanovich J, Thomas MA. Managing breast cancer in younger women: challenges and solutions. BREAST CANCER-TARGETS AND THERAPY 2015; 8:1-12. [PMID: 26730210 PMCID: PMC4694614 DOI: 10.2147/bctt.s68848] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Breast cancer in young women is relatively rare compared to breast cancer occurring in older women. Younger women diagnosed with breast cancer also tend to have a more aggressive biology and consequently a poorer prognosis than older women. In addition, they face unique challenges such as diminished fertility from premature ovarian failure, extended survivorship periods and its attendant problems, and the psychosocial impact of diagnosis, while still raising families. It is therefore imperative to recognize the unique issues that younger women face, and plan management in a multidisciplinary fashion to optimize clinical outcomes. This paper discusses the challenges of breast cancer management for young women, as well as specific issues to consider in diagnosis, treatment, and follow-up of such patients.
Collapse
Affiliation(s)
- Foluso O Ademuyiwa
- Department of Medicine, Washington University in St Louis School of Medicine, St Louis, MO, USA
| | - Amy Cyr
- Department of Surgery, Washington University in St Louis School of Medicine, St Louis, MO, USA
| | - Jennifer Ivanovich
- Department of Surgery, Washington University in St Louis School of Medicine, St Louis, MO, USA
| | - Maria A Thomas
- Department of Radiation Oncology, Washington University in St Louis School of Medicine, St Louis, MO, USA
| |
Collapse
|
31
|
Albright CM, Wenstrom KD. Malignancies in pregnancy. Best Pract Res Clin Obstet Gynaecol 2015; 33:2-18. [PMID: 26542928 DOI: 10.1016/j.bpobgyn.2015.10.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 10/09/2015] [Indexed: 12/13/2022]
Abstract
Malignancy complicating pregnancy is fortunately rare, affecting one in 1000 to one in 1500 pregnancies. Optimal treatment involves balancing the benefit of treatment for the mother while minimizing harm to the fetus. This balance is dependent on the extent of the disease, the recommended course of treatment, and the gestational age at which treatment is considered. Both surgery and chemotherapy are generally safe in pregnancy, whereas radiation therapy is relatively contraindicated. Iatrogenic prematurity is the most common pregnancy complication, as infants are often delivered for maternal benefit. In general, however, survival does not differ from the nonpregnant population. These patients require a multidisciplinary approach for management with providers having experience in caring for these complex patients. The aim of this review was to provide an overview for obstetricians of the diagnosis and management of malignancy in pregnancy.
Collapse
Affiliation(s)
- Catherine M Albright
- Division of Maternal Fetal Medicine, Brown University, Women and Infants Hospital, 101 Dudley Street, Providence, RI 02905, USA.
| | - Katharine D Wenstrom
- Division of Maternal Fetal Medicine, Brown University, Women and Infants Hospital, 101 Dudley Street, Providence, RI 02905, USA.
| |
Collapse
|
32
|
Ribnikar D, Ribeiro JM, Pinto D, Sousa B, Pinto AC, Gomes E, Moser EC, Cardoso MJ, Cardoso F. Breast cancer under age 40: a different approach. Curr Treat Options Oncol 2015; 16:16. [PMID: 25796377 DOI: 10.1007/s11864-015-0334-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Women<40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age<40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC<40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient's comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in presence of visceral metastases, unless there is concern or proof of endocrine resistance or there is a need for rapid disease response and/or symptom control. Recommendations for chemotherapy (CT) should not differ from those for older patients with the same characteristics of the metastatic disease and its extent. Young age by itself should not be an indication to prescribe more intensive and combination CT regimens over the sequential use of monotherapy. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) represent an important group of promising drugs in managing patients with breast cancer susceptibility gene (BRCA)-1- or BRCA-2-associated BC. Specific age-related side effects of systemic treatment (e.g., menopausal symptoms, change in body image, bone morbidity, cognitive function impairment, fertility damage, sexual dysfunction) and the social impact of diagnosis and treatment (job discrimination, taking care for children) should also be carefully addressed when planning systemic long-lasting therapy, such as endocrine therapy. Survivorship concerns for young women are different compared to older women, including issues of fertility, preservation, and pregnancy.
Collapse
Affiliation(s)
- D Ribnikar
- Medical Oncology Department, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | | | | | | | | | | | | | | | | |
Collapse
|
33
|
Pianca N, Shafiei M, George M. Trastuzumab Exposure in Early Pregnancy for a Young Lady With Locally Invasive Breast Cancer. World J Oncol 2015; 6:381-382. [PMID: 28983334 PMCID: PMC5624665 DOI: 10.14740/wjon919w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2015] [Indexed: 11/11/2022] Open
Abstract
Due to the lack of literature on the effects of trastuzumab in pregnancy, an interest has been taken in a patient that incidentally became pregnant while on adjuvant treatment in the first trimester following diagnosis of locally advanced breast cancer.
Collapse
Affiliation(s)
- Natasha Pianca
- Department of Medical Oncology, Northwest Regional Cancer Centre, Tamworth, Australia
| | - Mohsen Shafiei
- Department of Medical Oncology, Northwest Regional Cancer Centre, Tamworth, Australia
| | - Mathew George
- Department of Medical Oncology, Northwest Regional Cancer Centre, Tamworth, Australia
| |
Collapse
|
34
|
Lambertini M, Peccatori FA, Azim HA. Targeted agents for cancer treatment during pregnancy. Cancer Treat Rev 2015; 41:301-9. [DOI: 10.1016/j.ctrv.2015.03.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 03/06/2015] [Indexed: 02/07/2023]
|
35
|
Amant F, Han SN, Gziri MM, Vandenbroucke T, Verheecke M, Van Calsteren K. Management of cancer in pregnancy. Best Pract Res Clin Obstet Gynaecol 2015; 29:741-53. [PMID: 25797199 DOI: 10.1016/j.bpobgyn.2015.02.006] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Revised: 02/18/2015] [Accepted: 02/23/2015] [Indexed: 12/20/2022]
Abstract
A multidisciplinary discussion is necessary to tackle a complex and infrequent medical problem such as cancer occurring during pregnancy. Pregnancy does not predispose to cancer, but cancers occurring in women of reproductive age are encountered during pregnancy. Ultrasonography and magnetic resonance imaging are the preferred staging examinations, but also a sentinel node staging procedure is possible during pregnancy. Standard cancer treatment is aimed for. Operations can safely be performed during pregnancy, but surgery of genital cancers can be challenging. The observation that chemotherapy administered during the second or third trimester of pregnancy, that is, after the period of organogenesis, has little effect on the long-term outcome of children adds to the therapeutic armamentarium during pregnancy. Cancer treatment during pregnancy adds in the continuation of the pregnancy and the prevention of prematurity.
Collapse
Affiliation(s)
- Frédéric Amant
- Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium.
| | - Sileny N Han
- Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium
| | - Mina Mhallem Gziri
- Department of Obstetrics and Gynecology, Cliniques Universitaires St Luc, UCL, Brussels, Belgium
| | - Tineke Vandenbroucke
- Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium
| | - Magali Verheecke
- Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Department of Oncology, KU Leuven, Leuven, Belgium
| | - Kristel Van Calsteren
- Department of Obstetrics and Gynecology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| |
Collapse
|
36
|
Zardavas D, Ades F, de Azambuja E. Clinical practice-changing trials: the HERA study paradigm. Expert Rev Anticancer Ther 2014; 13:1249-56. [DOI: 10.1586/14737140.2013.848168] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- Dimitrios Zardavas
- Medical Oncology Department, Institut Jules Bordet,
Br.E.A.S.T. Data Centre Brussels, Blvd de Waterloo, 121 (7th Floor), 1000 Brussels, Belgium
| | - Felipe Ades
- Medical Oncology Department, Institut Jules Bordet,
Br.E.A.S.T. Data Centre Brussels, Blvd de Waterloo, 121 (7th Floor), 1000 Brussels, Belgium
| | - Evandro de Azambuja
- Medical Oncology Department, Institut Jules Bordet,
Br.E.A.S.T. Data Centre Brussels, Blvd de Waterloo, 121 (7th Floor), 1000 Brussels, Belgium
| |
Collapse
|
37
|
Abstract
Approximately 1 in 1,000-2,000 pregnancies are complicated by cancer. Today, different treatment options are considered as safe during pregnancy: chemotherapy, radiotherapy, surgery, or a combination of these. Surgery is considered safe during all trimesters of pregnancy; radiotherapy can be administered during the first and the second trimester, and chemotherapy after the first trimester of pregnancy. The placenta, acting as a barrier between the mother and the fetus, plays a key role in the safe administration of chemotherapy during pregnancy. A few studies have investigated the short- as well as the long-term health, general development, and cognitive and cardiac outcomes on children exposed to chemotherapy in utero. In general, these results were reassuring. Nevertheless, better safety data are required. This means data with longer follow-up periods and comparison with appropriate control groups. Moreover, important biasing factors should be taken into account when interpreting these results. Firstly, a great proportion of children were born prematurely due to the maternal condition. Preterm birth in general has been associated with cognitive impairment. Secondly, cancer during pregnancy is clearly a stressful situation, and maternal stress is associated with attention deficits. In sum, we state that chemotherapy can be administered safely after the first trimester of pregnancy. Moreover, iatrogenic prematurity in order to start postpartum administration of chemotherapy should be avoided. Nonetheless, decisions concerning treatment in these specific cases should always be made in a multidisciplinary setting with internationally recognized expertise in the coexistence of cancer and pregnancy.
Collapse
Affiliation(s)
- Jana Dekrem
- Lab of Experimental Gynaecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium
| | | | | |
Collapse
|
38
|
Zagouri F, Psaltopoulou T, Dimitrakakis C, Bartsch R, Dimopoulos MA. Challenges in managing breast cancer during pregnancy. J Thorac Dis 2013; 5 Suppl 1:S62-7. [PMID: 23819029 DOI: 10.3978/j.issn.2072-1439.2013.05.21] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Accepted: 05/28/2013] [Indexed: 12/13/2022]
Abstract
Pregnancy-associated breast cancer (PABC) is defined as breast cancer occurring anytime during gestation, lactation or within one year after delivery. The optimal management of pregnant women with breast cancer is challenging and not well established; the main concern is the effect of the drugs on the developing fetus and long-term complications after in utero exposure to anti-cancer drugs. Surgical resection is the mainstay of treatment for early breast cancer diagnosed during pregnancy. Modified radical mastectomy is standard of care in first trimester, whereas breast-conserving surgery (lumpectomy with lymph node dissection) can be performed preferably in the second and third trimester. Of note, breast-conserving surgery is not contraindicated per se during the first trimester, but owing to the potential impact of delaying radiotherapy. Radiation therapy is not favored during pregnancy. Moreover, tamoxifen is contraindicated during pregnancy; the agent has been associated with birth defects in up to 20% of exposures. Chemotherapy is generally contraindicated during the first trimester because of the possible damage to organogenesis. Anthracyclines-based regimens are the most widely used is breast cancer treatment and were been shown to be associated with favourable safety profile when administered during pregnancy. As for taxanes, more limited data is available. The use of trastuzumab is contraindicated during pregnancy, given the apparent risk of oligo- and/or anhydramnios as well as the unknown long-term sequelae on the fetus. It is obvious that, diagnosis of breast cancer during pregnancy adds complexity to cancer treatment recommendations. In all cases, a multidisciplinary therapeutic approach among obstetricians, gynaecologists, surgical oncologists, radiation oncologists, medical oncologists, pediatricians and hematologists is clearly warranted.
Collapse
Affiliation(s)
- Flora Zagouri
- Department of Clinical Therapeutics, Alexandra Hospital, Medical School, University of Athens, Athens, Greece; ; Comprehensive Cancer Center Vienna, Department of Medicine I/Division of Oncology, Medical University of Vienna, Austria
| | | | | | | | | |
Collapse
|
39
|
Meisel JL, Economy KE, Calvillo KZ, Schapira L, Tung NM, Gelber S, Kereakoglow S, Partridge AH, Mayer EL. Contemporary multidisciplinary treatment of pregnancy-associated breast cancer. SPRINGERPLUS 2013; 2:297. [PMID: 23888269 PMCID: PMC3710403 DOI: 10.1186/2193-1801-2-297] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Accepted: 06/20/2013] [Indexed: 11/13/2022]
Abstract
Breast cancer diagnosed during pregnancy poses unique challenges. Application of standard treatment algorithms is limited by lack of level I evidence from randomized trials. This study describes contemporary multidisciplinary treatment of pregnancy-associated breast cancer (PABC) in an academic setting and explores early maternal and fetal outcomes. A search of the Dana-Farber/Harvard Cancer Center clinical databases was performed to identify PABC cases. Sociodemographic, disease, pregnancy, and treatment information, as well as data on short-term maternal and fetal outcomes, were collected through retrospective chart review. 74 patients were identified, the majority with early-stage breast cancer. Most (73.5%) underwent surgical resection during pregnancy, including 40% with sentinel lymph node biopsy and 32% with immediate reconstruction. A total of 36 patients received anthracycline-based chemotherapy during pregnancy; of those, almost 20% were on a dose-dense schedule and 8.3% also received paclitaxel. 68 patients delivered liveborn infants; over half were delivered preterm (< 37 weeks), most scheduled to allow further maternal cancer therapy. For the infants with available data, all had normal Apgar scores and over 90% had birth weight >10th percentile. The rate of fetal malformations (4.4%) was not different than expected population rate. Within a multidisciplinary academic setting, PABC treatment followed contemporary algorithms without apparent increase in maternal or fetal adverse outcomes. A considerable number of preterm deliveries were observed, the majority planned to facilitate cancer therapy. Continued attention to maternal and fetal outcomes after PABC is required to determine the benefit of this delivery strategy.
Collapse
|
40
|
Lambertini M, Anserini P, Levaggi A, Poggio F, Del Mastro L. Fertility counseling of young breast cancer patients. J Thorac Dis 2013; 5 Suppl 1:S68-80. [PMID: 23819030 DOI: 10.3978/j.issn.2072-1439.2013.05.22] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2013] [Accepted: 05/29/2013] [Indexed: 12/11/2022]
Abstract
Approximately 6% of women with breast cancer are diagnosed before the age of 40. Young age is an independent predictor of adverse outcome and most young breast cancer patients receive systemic treatment with chemotherapy, hormonal therapy or both. The loss or impairment of fertility is a potential side effect of antineoplastic treatments. Due to the rising trend to delaying pregnancy in life, an increasing proportion of young cancer patients who are yet to have a pregnancy will face the problem of iatrogenic menopause in the future. The incidence of anticancer-treatment-related ovarian failure depends on the type of chemotherapy regimen administered, the use of tamoxifen and the age of patients. It rises with increasing age, in the range of 22-61% and 61-97% in women aged <40 years and >40 years respectively. Although there is a clear trend to increasing incidence of ovarian failure with the rise in aging, there may be a small proportion of patients who became amenorrhoeic despite the very young age, thus indicating that also individual factors still unknown may affect the probability of treatment-related ovarian failure. A prompt referral of patients to reproductive counseling and a multidisciplinary team including Oncology and Reproductive Units are essential to face the management of fertility issues in cancer patients. Fertility counseling should include a detailed description of all the available techniques to preserve fertility. The main available fertility preservation techniques, standard and experimental, for young breast cancer patients include: temporary ovarian suppression during chemotherapy with gonadotropin-releasing hormone analogues, embryo cryopreservation, cryopreservation of oocytes and cryopreservation of ovarian tissue. Research efforts are still necessary to improve the efficacy and safety of the available fertility preservation strategies as well as an efficient collaboration between oncologists and gynecologists is necessary to improve patients' access to the strategies themselves.
Collapse
|
41
|
Le trastuzumab dans le traitement adjuvant du cancer du sein. Presse Med 2013; 42:1069-80. [DOI: 10.1016/j.lpm.2013.01.054] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Revised: 12/20/2012] [Accepted: 01/02/2013] [Indexed: 11/22/2022] Open
|
42
|
Sarno MA, Mancari R, Azim HA, Colombo N, Peccatori FA. Are monoclonal antibodies a safe treatment for cancer during pregnancy? Immunotherapy 2013; 5:733-41. [DOI: 10.2217/imt.13.64] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Monoclonal antibodies (mAbs) are the cornerstone of the treatment of several types of tumors, but their use in pregnant women is not clearly defined. Here, we report and analyze all available data on mAb treatment in pregnant cancer patients. A literature search was performed from 2000 until January 2013 and all articles addressing safety of mAbs during pregnancy were reviewed. We found very few data on the use of bevacizumab in pregnant women. However, owing to its antiangiogenic effects and possible consequences on fetal development, it should be avoided during pregnancy. Trastuzumab administration has been associated with an elevated incidence of oligohydramnios and poor neonatal outcomes, particularly when prescribed after the first trimester for repeated infusions, and therefore it is not recommended. Rituximab does not seem to be teratogenic, but a transient prolonged neutropenia in the newborns was reported, without major infectious consequences in most cases. Few data are available about other mAbs, and hence their use during pregnancy remains discouraged.
Collapse
Affiliation(s)
- Maria Anna Sarno
- Fertility & Procreation Unit in Oncology, Gynecologic Oncology Division, European Institute of Oncology, Via Ripamonti 435, 20141 Milan Italy
| | - Rosanna Mancari
- Division of Gynecologic Oncology, European Institute of Oncology, Milan Italy
| | - Hatem A Azim
- Department of Medicine, BrEAST Data Centre, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Nicoletta Colombo
- Division of Gynecologic Oncology, European Institute of Oncology, Milan Italy
| | - Fedro A Peccatori
- Fertility & Procreation Unit in Oncology, Gynecologic Oncology Division, European Institute of Oncology, Via Ripamonti 435, 20141 Milan Italy
| |
Collapse
|
43
|
Peccatori FA, Azim HA, Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, Pentheroudakis G. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 Suppl 6:vi160-70. [PMID: 23813932 DOI: 10.1093/annonc/mdt199] [Citation(s) in RCA: 495] [Impact Index Per Article: 41.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Affiliation(s)
- F A Peccatori
- Fertility and Procreation Unit, Division of Gynaecologic Oncology, European Institute of Oncology, Milan, Italy
| | | | | | | | | | | | | | | |
Collapse
|
44
|
Abstract
CONTEXT The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. EVIDENCE ACQUISITION PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. EVIDENCE SYNTHESIS KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. CONCLUSIONS Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.
Collapse
Affiliation(s)
- Maya B Lodish
- Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Pediatric Endocrinology Inter-Institute Training Program, National Institutes of Health, Bethesda, MD 20892, USA.
| |
Collapse
|
45
|
Han SN, Amant F. Trastuzumab, lapatinib and bevacizumab during pregnancy. BREAST CANCER MANAGEMENT 2013. [DOI: 10.2217/bmt.12.51] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Sileny N Han
- Multidisciplinary Breast Cancer Centre, Leuven Cancer Institute (LKI), University Hospitals Leuven, Belgium
| | - Frédéric Amant
- Multidisciplinary Breast Cancer Centre, Leuven Cancer Institute (LKI), University Hospitals Leuven, Belgium
| |
Collapse
|
46
|
Trastuzumab administration during pregnancy: a systematic review and meta-analysis. Breast Cancer Res Treat 2012; 137:349-57. [DOI: 10.1007/s10549-012-2368-y] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Accepted: 11/30/2012] [Indexed: 01/01/2023]
|
47
|
Abstract
Most young breast cancer survivors consider reproductive issues to be of great importance, but many questions remain undervalued and unanswered. Overall, available data support the safety and feasibility of pregnancy and breastfeeding after breast cancer. The accuracy of the evidence is however limited by: i) the retrospective and frequently incomplete population-based nature of the data, ii) data not representing the entire population, iii) patient-related effects, iv) underpowered sample size, and v) lack of control for biological factors and risk determinants. We review the available evidence in light of these limitations which outline the need for prospective data collection and focused priority research.
Collapse
Affiliation(s)
- Olivia Pagani
- Institute of Oncology of Southern Switzerland, Breast Unit of Southern Switzerland, Ospedale san Giovanni, Bellinzona, Switzerland
| | | |
Collapse
|
48
|
Loibl S, Han SN, Amant F. Being Pregnant and Diagnosed with Breast Cancer. ACTA ACUST UNITED AC 2012; 7:204-209. [PMID: 22872793 DOI: 10.1159/000339674] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Breast cancer during pregnancy (BCP) is an important subgroup within the young and very young breast cancer patients. It accounts for about 1% of all breast cancers. Due to an increased awareness, the attitude towards breast cancer during pregnancy has changed and, today, women with BCP are more likely to receive standard chemotherapy and have a term delivery instead of being advised to interrupt the pregnancy or undergo an early preterm delivery. This increased knowledge is based on small cohort studies and international collaborations such as the registry by the German Breast Group for BCP and the initiative of the European Society of Gynaecological Oncology (ESGO). Guidelines and recommendations such as the German guidelines by the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, www.ago-online.org) and the National Comprehensive Cancer Network (NCCN) guidelines include recommendations for BCP. In general, surgery and chemotherapy (beyond the 13th week of gestation) can be safely performed during pregnancy. Chemotherapy should follow the treatment recommendations for breast cancer in young women. Trastuzumab, endocrine treatment, and radiotherapy are not indicated during pregnancy. Preterm delivery should be avoided as far as possible because it bears a higher risk of infant morbidity and mortality. The treatment of BCP should be planned within a multidisciplinary team including perinatologists, obstetricians and neonatologists.
Collapse
|