• Breast cancer
• Histopathology
• Neoadjuvant chemotherapy
• Prognosis
• Receptor conversion

• Humans
• Female
• Neoadjuvant Therapy/methods
• Breast Neoplasms/mortality
• Breast Neoplasms/pathology
• Breast Neoplasms/drug therapy
• Middle Aged
• Retrospective Studies
• Prognosis
• Adult
• Aged
• Receptors, Estrogen/metabolism
• Receptors, Progesterone/metabolism
• Receptor, ErbB-2/metabolism
• Chemotherapy, Adjuvant
• Ki-67 Antigen/metabolism
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use

• ER
• PR
• breast
• cancer
• discordance
• metastatic
• receptor

• Biomarkers
• Breast cancer
• Neoadjuvant chemotherapy
• Tumor size change
• pCR

• Humans
• Female
• Breast Neoplasms/pathology
• Biomarkers, Tumor/analysis
• Ki-67 Antigen/analysis
• Neoadjuvant Therapy
• Prognosis
• ErbB Receptors
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Receptor, ErbB-2/metabolism
• Retrospective Studies

• 82272049 National Natural Science Foundation of China
• 82272049 National Natural Science Foundation of China

• Breast neoplasms
• ErbB-2 receptor
• Estrogen receptors
• Ki-67 antigen
• Neoadjuvant therapy
• Progesterone receptors
• Tumor-infiltrating lymphocytes

• Humans
• Female
• Neoadjuvant Therapy
• Ki-67 Antigen
• Receptor, ErbB-2/metabolism
• Breast Neoplasms/pathology
• Neoplasm Grading
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Chemotherapy, Adjuvant
• Prognosis

• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

• Breast cancer
• Estrogen receptor
• Neoadjuvant chemotherapy
• Pathologic complete response
• Prognosis

• Humans
• Female
• Breast Neoplasms/drug therapy
• Receptors, Estrogen
• Neoadjuvant Therapy
• Prognosis
• Disease-Free Survival

• LQ20H160031 Natural Science Foundation of Zhejiang Province

• Estrogen receptor discordance
• postsurgery
• pre neoadjuvant chemotherapy
• progesterone receptor discordance
• staining pattern

As the most common cancer in women, breast cancer is the leading cause of death. Most patients are initially diagnosed as stage I-III. Among those without distant metastases, 64% are local tumors and 27% are regional tumors. Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy (NACT). It is worth noting that the status of tumor cell biomarkers is not consistently static. Endocrine-related estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa, especially in luminal B subtype after NACT. In addition, determination of HER2 status currently mainly relies on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), but FISH is commonly used when the result of IHC is uncertain. HER2 is regarded as negative when the IHC result is 0/1+ without the addition of FISH. To the best of our knowledge, this is the first report of a case harboring HER2 status transformation and IHC1+ with positive amplification by FISH after NACT.

A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup. Biopsies of the right breast lesion and axillary lymph nodes were obtained. The results pointed to invasive ductal carcinoma with the IHC result for ER (80%), PR (60%), Ki-67 (20%) and ambiguous expression of HER2 (IHC 2+) with negative amplification by FISH (HER2/CEP17 ratio of 1.13). She underwent surgery after NACT. The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm × 0.8 cm × 0.5 cm and had spread to one of fifteen dissected lymph nodes. Retesting of the specimen showed that the tumor was positive for ER (2+, 85%) and PR (2+, 10%) but negative for HER2 by IHC (1+). Also Ki-67 had dropped to 2%. The patient was regularly monitored every 3 mo without evidence of recurrence.

Biomarker status should be reassessed after NACT especially in luminal subtypes.

• Carcinoma
• Ductal
• Breast
• Neoadjuvant therapy
• Biomarkers, Tumor
• Case report

The discordance of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 cell nuclear proliferation antigen status in patients with locally advanced breast cancer pre- and post-neoadjuvant chemotherapy (NAC) is quite common. This study aimed to assess the frequency of changes in receptor status after NAC in patients with invasive ductal breast cancer and the prognostic impact of such changes.

The study comprised 670 patients who were diagnosed with invasive ductal breast carcinoma and treated with both NAC and surgery from 2012–2017. Hormone receptor (HR; including ER and PR), HER2, and Ki-67 status was assessed before NAC and in residual invasive tumor cells of the surgical specimens. The prognostic impact of receptor conversions in breast cancer patients treated with NAC was evaluated in this retrospective study.

The conversion of ER was related to overall survival (OS; P=0.008) and disease-free survival (DFS; P=0.004). Patients whose ER status was always positive had the best prognosis, and those who were always negative had the worst prognosis. Similar results were also found for PR status, as the conversion of PR status was also related to OS (P<0.001) and DFS (P<0.001). At the same time, the conversion of Ki-67 status was related to OS (P=0.042) and DFS (P=0.037), and patients whose Ki-67 status was ≤20% persistently after NAC had the best survival among the 4 groups, while those whose Ki-67 status changed from ≤20% to >20% after NAC had the worst survival. Nevertheless, there was no statistical significance in the conversion of HER2 status. In multivariate Cox regression analyses, PR conversion and post-neoadjuvant pathological lymph node stage (ypN) were independent prognostic factors for DFS (P=0.008, <0.001) and OS (P=0.002, <0.001).

Changes in receptor status between pre-treatment and residual disease after NAC are common. Moreover, these alterations have an impact on the survival outcome of invasive ductal breast cancer patients. Thus, receptor status should be re-evaluated routinely before and after NAC to guide individualized treatment.

• Neoadjuvant chemotherapy (NAC)
• breast cancer
• prognostic impact
• receptor conversions

The prognostic impact of neoadjuvant chemotherapy (NAC) on the receptor expression status in patients with locally advanced breast cancer (LABC) is still not fully understood. We aimed to evaluate the changes in hormone (estrogen and progesterone) receptor (HR) and human epidermal growth factor receptor 2 (HER2) status post-NAC and their correlation with survival.

Patients with LABC who have received NAC between 2008 and 2015 and have been followed up till December 2019 at the Oncology Center, King Saud University, KSA were analyzed retrospectively. biomarker analysis of ER, PR & HER2 were done using immunohistochemistry (IHC) and Fluorescent in situ hybridization.

Ninety-one patients fulfilled the inclusion criteria. HR status changed in 21(23.1%) patients, with a significant difference between patients with stable receptors and those with any receptor conversion; p = 0.000. Five (5.5%) initially HER2 negative tumors became HER2 positive and 10 (11%) initially HER2 positive tumors became HER2 negative after NAC. The difference in HER2 expression level before and after NAC was not statistically significant (p = 0.302). Univariate analysis relating patients’ characteristics and 10-years disease-free survival (DFS) showed only significant correlations with the expressions of ER, PR, and any receptor conversion, (ER and/or PR) p< 0.001, p< 0.001, and p = 0.001; respectively. In the univariate analysis, none of the clinicopathological features showed a significant correlation with the OS except for the molecular subtypes P<0.001.

Patients with LABC have significant changes in the ER and PR receptor status following NAC. Post-NAC expressions change of ER and PR (ER and/or PR) are correlated to DFS. Retesting of the hormone receptors should be considered after NAC in Saudi patients with LABC.

The large variation in histologic grading of invasive breast cancer (IBC) that has been reported likely influences tailoring adjuvant therapy. The role of grading in therapeutic decision-making in daily practice, was evaluated using the Dutch national guidelines for IBC-management.

Synoptic reports of IBC resection-specimens, obtained between 2013 and 2016, were extracted from the nationwide Dutch Pathology Registry, and linked to treatment-data from the Netherlands Cancer Registry. The relevance of grading for adjuvant chemotherapy (aCT) was quantified by identifying patients for whom grade was the determinative factor. In addition, the relation between grade and aCT-administration was evaluated by multivariate logistic regression for patients with a guideline-aCT-indication.

30,843 patients were included. Applying the guideline that was valid between 2013 and 2016, grade was the determinative factor for the aCT-indication in 7744 (25.1%) patients, a percentage that even increased according to the current guideline where grade would be decisive for aCT in 10,869 (35.2%) patients. Also in current practice, the indication for adjuvant endocrine therapy (aET) would be based on grade in 9173 (29.7%) patients. Finally, as patients with lower-grade tumors receive aCT significantly less often, grade was also decisive in tailoring aCT de-escalation.

In the largest study published so far we illustrate the increasing importance of histologic grade in tailoring adjuvant systemic breast cancer therapy. Next to playing a key-role in aCT-indication and de-escalation, the role of grading has expanded to the indication for aET. Optimizing histologic grading by pathologists is urgently needed to diminish the risk of worse patient outcome due to non-optimal treatment.

The online version contains supplementary material available at 10.1007/s10549-021-06098-7.

• Adjuvant systemic treatment
• Guideline adherence
• Histologic grade
• Invasive breast cancer
• Real-world data

Currently, the indication for neoadjuvant chemotherapy is increasing in the treatment of breast cancer. Variability in the expression of biomarkers following neoadjuvant treatment has been observed, which could be accompanied by changes in the adjuvant treatment.

The primary objective was to evaluate the variability of biomarkers prior to and following neoadjuvant therapy. Secondary objectives were to determine which tumour subtype (as determined by immunohistochemical markers) most frequently achieved pathological complete response (pCR); whether the biomarker variation resulted in a change in immunophenotype and subsequently modification to the adjuvant treatment.

A retrospective observational analysis was carried out on patients with a diagnosis of breast cancer who had neoadjuvant therapy prior to surgery in the Breast Care Service of the Buenos Aires British Hospital between January 2009 and June 2020.

One hundred and seventy-two patients were included. The pCR rate was 28.5%. The tumour immunophenotype that achieved pCR most frequently was the hormone receptor negative /HER2+ group with a value of 85.2%. The analysis was carried out on the 123 patients with residual disease. The observed variability for oestrogen receptors (ER) was 8.9%, for progesterone receptors (PR), 29.9% and for HER2, 13.8%. These changes were statistically significant. There were changes to the tumour immunophenotype in 26 cases (21.1%) with modifications to the adjuvant treatment in nine of these (34.6%; 7.3% of all tumours with residual disease).

In this study, we observed statistically significant variability in the expression of ER, PR and HER2 prior to and following neoadjuvant treatment, which identified modifications in the tumour immunophenotype in 21.1%, and changes to the adjuvant treatment in 7.3% of all tumours with residual disease, justifying the re-assay of biomarkers in the surgical specimen.

• HER2
• adjuvant
• hormonal receptors
• neoadjuvant
• pathological complete response
• variability

• Carcinoma
• Estrogen receptor
• Progesterone receptor
• Response
• Survival

• Chemotherapy
• DCE-MRI
• DW-MRI
• Forecasting
• Simulation

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Breast Neoplasms/diagnosis
• Breast Neoplasms/therapy
• Data Analysis
• Disease Management
• Female
• Humans
• Image Processing, Computer-Assisted
• Magnetic Resonance Imaging/methods
• Middle Aged
• Models, Theoretical
• Monte Carlo Method
• Neoadjuvant Therapy/adverse effects
• Neoadjuvant Therapy/methods
• Precision Medicine/methods
• Treatment Outcome

• U24 CA226110 NCI NIH HHS
• U01 CA154602 NCI NIH HHS
• T32 EB007507 NIBIB NIH HHS
• R01 CA240589 NCI NIH HHS
• R01 CA186193 NCI NIH HHS
• U01 CA174706 NCI NIH HHS

• Biomarkers
• Breast neoplasms
• Heterogeneity
• Immunohistochemistry
• Neoadjuvant therapy

• breast cancer
• estrogen receptor
• neoadjuvant chemotherapy
• progesterone receptor
• triple negative

Patient management of invasive breast cancer (IBC) is to a large extent based on hormone- and HER2-receptor assessment. High-quality, reliable receptor assessment is of key importance as false results may lead to under- or overtreatment of patients. Surveillance of case-mix adjusted positivity rates has been suggested as a tool to identify laboratories with insufficient testing assays, as this covers the whole process of receptor assessment and enables laboratories to benchmark their positivity rates against other laboratories. We studied laboratory-specific variation in hormone- and HER2 positivity rates of 33,046 breast cancer patients using real-life nationwide data.

All synoptic pathology reports of IBC resection-specimens, obtained between 2013 and 2016, were retrieved from the nationwide Dutch pathology registry (PALGA). Absolute and case-mix adjusted receptor positivity rates were compared to the mean national proportion and presented in funnel plots in separate analyses for estrogen (ER), progesterone (PR) and HER2. Case-mix adjustment was performed by multivariable logistic regression.

33,794 IBC lesions from 33,046 patients of 39 pathology laboratories were included. After case-mix adjustment, mean positivity rates were 87.2% for ER (range 80.4–94.3), 71.3% for PR (62.5–77.5%), and 9.9% for HER2 (5.5–12.7%). Overall, 14 (35.9%), 17 (43.6%) and 11 (28.2%) laboratories showed positivity rates outside the 95% confidence interval for ER, PR and HER2, respectively.

This nationwide study shows that absolute variation in hormone- and HER2-receptor positivity rates between Dutch pathology laboratories is limited. Yet, the considerable number of outlying laboratories shows that there is still need for improvement. Continuous monitoring and benchmarking of positivity rates may help to realize this.

• HER2
• Hormone receptor
• Inter-laboratory variation
• Invasive breast cancer
• PALGA
• Pathology

• Breast cancer
• Diagnostics
• Discordance
• Estrogen
• Human epidermal growth factor receptor 2
• Progesterone