Impact of shifting of hormonal receptor and human epidermal growth factor receptor 2 on survival of non-metastatic breast cancer

Introduction: Tumor heterogeneity presents a significant impediment to identifying appropriate treatments for patients. Genetic mutations and hormone receptors are frequently used as a guide for selecting appropriate targeted or hormonal therapies, however it is possible that these markers may change over time, leading to reduced effectiveness of these treatments. In this study, we review the results of serial and paired biopsies to identify receptor switch in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as well as to identify changes in clinically relevant mutations, including spatial and temporal heterogeneity. Methods: We identified a total of 237 patients initially presenting with ER+/HER2 negative breast cancer and who had multiple biopsies during the course of their treatment, including at least one in the metastatic setting. ER, PR, and HER2 status for each of these serial biopsies was gathered from chart reviews. HER2 results by both IHC and FISH were collected. PIK3CA mutations were also assessed by Snapshot utilizing multiplexed PCR of common hotspot mutations using DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue. Results: From a total of 213 patients with known ER status for multiple serial biopsies, we identified 9.4% (N=20) who had at least one change in ER status over time. From a total of 198 patients who had documented PR status for multiple biopsies, 40.4% (N=80) had at least one change in PR status. Changes in HER2 status were similarly assessed, with 6.7% of patients having at least one change by IHC and 4.4% of patients having at least one change by FISH. Of those patients exhibiting changes in ER status, 6 were noted to have multiple changes over time. Of those with changes in PR status, 18 had multiple changes over time. Changes in hormone receptor status were also noted to occur between serial biopsies in the metastatic setting. A total of 128 patients had ER results available for multiple metastatic specimens, of which 8.6% (N=11) had at least one change in ER status. A total of 116 patients had PR results available for multiple metastatic biopsies, of which 38.8% (N=45) had at least one change in PR status. Changes were also noted in the metastatic setting in HER2 (IHC) with a frequency of 8.7% and in HER2 (FISH) with a frequency of 4.7%. A subset of 108 patients were identified as harboring a mutation in PIK3CA. Within this population, 9.6% of patients had at least one change in ER status over time and 34.1% had at least one change in PR status. 9.0% exhibited at least one change in HER2 (IHC) and 6.5% in HER2 (FISH). Serial changes in genotype, from pre- and post-treatment biopsies, were also detected using NGS based Foundation Medicine platform, including acquired alterations in the ESR1 and PI3K pathway. Conclusion: Serial changes in hormone receptor status and mutation profile are not uncommon among patients initially diagnosed with ER+/HER2 negative breast cancer, and some patients have been noted to have multiple changes over time. Further studies are needed to understand the mechanistic underpinnings governing the emergence of these alterations and their relationship to therapeutic resistance in breast cancer. Citation Format: Henderson L, Brachtel E, Fitzgerald D, Gadd M, Specht M, Thabet A, Gurski J, Sgroi D, Moy B, Isakoff S, Bardia A, Juric D. Serial evolution of hormone receptor status and mutational profile among patients with metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-06-03.

Background: Hormone receptor (Estrogen receptor (ER), Progesterone receptor (PgR)) is an important biological marker for predicting prognosis and making effective treatment decisions. Discordance in these biomarkers between the primary tumor and recurrent lesions is reported frequently. However, it is not well known whether these biomarkers are affected by neoadjuvant chemotherapy and their impacts on outcomes still remain to be elucidated. The aim of the present study is to evaluate the changes in HR status after neoadjuvant chemotherapy in patients with operable breast cancer and their relationship with response to treatment and prognosis. Patients and Methods: Of 162 patients with stage II/III breast cancer patients receiving neoadjuvant chemotherapy from January 2005 to September 2012 at Keio University Hospital, 140 patients with non-pCR were analyzed. Patients were treated with sequential anthracycline and taxane. ER and PgR were assessed in both CNB performed prior to neoadjuvant chemotherapy and surgical samples. HR status was assessed by immunohistochemistry (IHC). ER/PgR status was determined using the Allred score and defined as positive when score was 3 and more. HR status was considered positive in cases of ER and/or PgR positivity. Pathological response criteria were classified as grade 0, 1, 2, or 3: grade 0 includes almost no change in cancer cells; grade 1 includes slight or marked changes in less than two thirds of area; grade 2 includes marked changes in more than two thirds of area; grade3 includes necrosis or disappearance of all tumor cells. Results: ER, PgR and HR positive rates before neoadjuvant chemotherapy were 72.9%, 67.1% and 76.4%, respectively. Changes in ER, PgR and HR status between CNB and surgical samples were 12.1% (4.3% gain; 7.8% loss), 17.1% (2.1% gain; 15.0% loss) and 9.3% (2.9% gain; 6.4% loss), respectively. In ER-discordant group, grade 2 rate of pathological response was significantly higher than ER- concordant group (61.1% vs. 30%, p=0.033), whereas there were no significant differences of pathological response between discordant and concordant group in PgR status. In the disease free survival (DFS), there were no significant difference between concordance and discordance group for ER, PgR and HR (p=0.216, 0.859, 0.233) after a median follow-up of 40.4 months. But patients with a loss in ER and/or HR status had a trend to a shorter DFS compared with the concordant ER and/or HR-positive group (p=0.169 and 0.154) Conclusions: After neoadjuvant chemotherapy, discordance of biomarkers was seen in 5-20%. The pathological response was significantly associated with the change in ER status. A loss in ER and/or HR status may affect a prognosis of breast cancer after neoadjuvant chemotherapy, but still need further investigation. Citation Format: Toshiaki Kurihara, Hanako Ueno, Masaru Takemae, Aiko Nagayama, Maiko Takahashi, Tetsu Hayashida, Hiromitsu Jinno, Yuko Kitagawa. Prognostic impact of discordance in hormone receptor status after the neoadjuvant chemotherapy in primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-49.

Neoadjuvant chemotherapy forms the initial modality of treatment for primarily inoperable locally advanced breast cancer (LABC). Breast cancer is characterized by cellular heterogeneity. A change in hormone receptor status after neoadjuvant chemotherapy (NACT) has important therapeutic and prognostic consequences. Data on the influence of neoadjuvant chemotherapy on estrogen receptors (ER) and progesterone receptors (PR) are limited. The primary objective of this study is to compare hormone receptor (HR) status before and after neoadjuvant chemotherapy (discordance) in Indian patients. The secondary objective is to study correlation between tumor response and hormone receptor expression. This is a descriptive study of 78 LABC patients who received neoadjuvant chemotherapy from October 2012 to October 2014. All patients who underwent core biopsy and ER/PR assessment before and after NACT were included in the study. Data was collected prospectively from each patient in a structured proforma. Patients were classified as Group A (ER+, PR+), Group B (ER+, PR-), Group C (ER-, PR+), Group D (ER-, PR-). The HR discordance rate & response to neoadjuvant chemotherapy was assessed. Total HR discordance rate was 21.7%. The ER discordance was 8.7% and PR discordance was 13%. PR positive to PR negative discordance was the predominant one. The pathological complete remission (pCR) rate of endocrine responsive patients was 10.2% and in the endocrine unresponsive group it was 13.8%. ER/PR status can change after chemotherapy, hence they need to be re-evaluated after neoadjuvant chemotherapy. This becomes therapeutically important when receptor negative becomes positive.

Background: Hormone receptors (HR) and Human Epidermal Growth Factor Receptor 2 (HER2) status are variables that significantly influence the treatment regimens chosen for each patient (pt). The main objective of this study present was to determine the incidence of HR status change pre- and post- neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). Methods: A single-centre study was retrospectively conducted at The Ottawa Hospital Cancer Centre looking at a group of 546 pts diagnosed with LABC from 2006-2015. A number of variables were observed including HR and HER2 status, tumor size and grade, regional lymph nodes involvement, presence of DCIS, treatment regimens. 'Positive to Negative' considered pts who were HR and/or HER2 positive pre-NAC and negative post-NAC, 'No Change' represented the pts whose pathology did not change before and after NAC, and 'Negative to Positive' characterized those pts whose HR and/or HER2 pathology was initially negative and became positive post-NAC. Wilcoxon signed-rank test for paired dichotomous variables has been performed in order to estimate statistical significance of changes in status of HR and HER2. To explore possible relationship between HR and HER2 status change and other factors we used Logistic regression method. Results: Of the 386 pts who were examined for Estrogen Receptor (ER) twice, 285 had positive status before surgery, after surgery there were 12 pts (3.11%*) with a 'Positive to Negative' change, 362 pts (93.78%) with no change, and 12 pts who represented a 'Negative to Positive' change. 254 of 378 pts, who had two tests for Progesterone Receptor (PR), had positive results at first time, and 29 (7.67%*) of those represented a 'Positive to Negative' change, there were 337 (89.15%) with no change, and 12 (3.17%) with a 'Negative to Positive' change. From 387 pts who were tested for HER2 before and after surgery, 105 had initially positive status. Of those, 12 (3.10%*) represented a 'Positive to Negative' change, there were 364 (94.06%) with 'No Change' and 11 (2.84%*) with a 'Negative to Positive' change. Logistic regression analysis did not reveal any significant factors that can predict changes in receptors` status. *-Statistically significant changes (p<0.001). The results are comparable with previously published works, which demonstrated changes in IHC status during treatment in metastatic disease (E.Amir, 2011) and a in patients with LABC (Y.Yang, 2013; R.Gahlaut, 2016). Results of comparative meta-analysis will be presented also. Conclusions: Our study shows that a change in HR and HER2 status is common in this population, indicating that close monitoring of biopsy results should be closely compared to surgical pathology specimens to determine a change in biomarkers, and therefore, a potential change in treatment regimen. None of analyzed factors can predict change in status of ER, PR, and HER2 after neoadjuvant treatment. Even though the incidence of change in status is small, the implications for accurate and personalized treatment are important and HR and HER2 testing should be performed as a routine practice on the biopsy and at the time of definitive surgery. Citation Format: Aseyev O, Simmonds L, Gertler M, Verma S. Incidence and implications for hormone receptor status change pre- and post- neoadjuvant chemotherapy for locally advanced breast cancer: A retrospective single-center cohort study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-12.

Background: Testing of biomarkers in biopsies is a critical driver of determining therapy in patients diagnosed with invasive breast cancer. In the past, open surgical biopsy was considered to be the gold standard, but has been supplanted by the less invasive core needle biopsy. It is therefore imperative to know if such biopsies are representative of disease existing within the entirety of the tumor. This is especially the case now that neoadjuvant therapy is offered to patients with early stage tumor prior to surgical excision. In order to confirm that core biopsies are sufficient to serve as the launch point for treatment decision, we have conducted a retrospective review to compare the biomarker results of core biopsies with their corresponding excisional specimens. Previous studies have contained a smaller sample size, thus this is the largest single-site study of its kind. Methods: Data from patients with invasive breast cancer diagnosed between 2006 and 2013 have been retrospectively studied. Results for estrogen receptor (ER), progesterone receptor (PR) and Her2 status were analyzed. When the core biopsy and excisional specimens are either both "positive" or both "negative," the pair is considered to be "concordant." Otherwise, the pair is categorized as "discordant." As per the current ASCO/CAP guideline, hormone receptor status (estrogen and progesterone receptors) is considered positive if there were at least 1% tumor cells positive for either ER or PR. Both IHC and FISH concordance are evaluated for Her2 status. Patients who received neoadjuvant therapy of any kind were excluded from this study. Results: A total of 571 pairs of data totaling 1142 samples were analyzed in this study. Concordance for ER status is 97%, and for PR status is 92%. Concordance for hormone receptor status (when results of ER and PR are combined) between core biopsy and excision is 99%. Concordance for Her2 status, using FISH as the gold standard is 99%. Discussion: Typically, tumors that are ER+ are often also PR+. Nevertheless, they are often treated the same with hormonal therapy whether ER+PR+, ER+PR-, or, less commonly, ER-PR+. Almost all laboratories perform both ER and PR as a standard testing protocol for all breast carcinomas. Therefore, the lower concordance rate for only PR status without taking into consideration ER result is less meaningful. This study shows very high concordance rates for hormone receptor and Her2 status between core needle biopsy and excisional specimens, reiterating that treatment of invasive breast cancers based on the marker results obtained from core needle biopsies is appropriate. Citation Format: Music J, Sahoo S. Correlation of predictive markers in invasive breast carcinoma in core and excision specimens: A retrospective review. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-35.

To investigate the prognostic value of positive-to-negative changes in hormone receptor (HR) status after neoadjuvant chemotherapy (NCT) in patients with HR-positive breast cancer. Data from 224 stage II-III breast cancer patients with positive HR status before NCT who had residual disease in the breast after NCT were collected. HR status of the residual tumors was retested after NCT. A survival analysis was performed in 214 patients with adjuvant endocrine therapy regardless of post-NCT HR status. The survival analysis also examined other clinical and pathologic variables. In total, 15.2 % of patients had a positive-to-negative change in HR status after NCT, and this change was observed more frequently in HER-2-positive tumors than HER-2-negative tumors (P = 0.001). In 214 patients who had been treated with adjuvant endocrine therapy regardless of post-NCT HR status, the alteration in HR status was an independent factor for the prediction of a poorer disease-free survival (P = 0.026) and overall survival (P < 0.001) in the adjuvant endocrine therapy patients. The 5-year disease-free survival and overall survival rates were 43.5 % and 59.8 %, respectively, in patients with HR status conversion and 67.8 % and 82.5 %, respectively, in patients whose HR status remained positive (log rank test P = 0.003 and P = 0.001). The switch of HR status after NCT is remarkable for HR-positive tumors. An HR-negative switch may identify patients who would benefit from alternative systemic therapies.

Introduction: Intratumoral hormone receptor (HR) heterogeneity may have implications for molecular classification of breast tumors which, in turn, may impact clinical decision making and epidemiologic research. Prior studies show that 10-20% of patients have discordant estrogen receptor (ER) or progesterone receptor (PR) status upon repeat assay. While technical factors contribute to this discordance, intratumoral HR heterogeneity may also play a role. We examined the association between intratumoral HR heterogeneity, measured at a single research laboratory, and clinical HR status, tumor characteristics and demographic variables. Methods: We used paraffin-embedded blocks from 932 invasive breast cancer cases, of which 497 were African-American, from the population-based Carolina Breast Cancer Study Phase 3, part of the African-American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Two to four 1mm tumor cores per case were assembled into tissue microarrays and stained for ER and PR at a single research laboratory. ER and PR status (positive: ≥1% positive tumor cells; negative: &amp;lt;1%) were assigned to each core by automated digital image analysis and ER and PR status were assigned to each case by core-to-case collapsing, using the weighted average of positive cells across all cores. Intratumoral heterogeneity status (i.e. ‘homogeneous’ vs. ‘heterogeneous’) was assigned based on ‘identical’ or ‘different’ HR status between cores from a single case. Multivariable logistic regression was used to evaluate the association between heterogeneity status and patient and tumor characteristics, overall and stratified by menopausal status. Clinical HR status (positive vs. negative) was abstracted from medical records and concordance between clinical and research ER and PR status were examined, overall and stratified by heterogeneity status. Results: Of 932 cases, 95 (10%) had ER heterogeneity while 149 (16%) had PR heterogeneity. Overall, there was high agreement between clinical and research ER status (93% concordance; 95% confidence interval (CI) 92-95%) and PR status (89%; 95%CI 87-91%), consistent with previously reported inter-laboratory concordance rates. However, agreement was lower in cases with intratumoral heterogeneity (ER: 74%; 95%CI 65-83% and PR: 61%; 95%CI 53-69%), relative to homogeneous cases (ER: 96%; 95%CI 95-97% and PR: 94%; 95%CI 92-96%). Obesity, defined as BMI≥30kg/m2, was associated with increased odds of ER heterogeneity (adjusted odds ratio (OR)obese vs. normal weight 1.76; 95%CI 0.95-3.29), with a stronger association among postmenopausal women (OR 2.52; 95%CI 1.14-5.56). High tumor grade was associated with increased odds of both ER and PR heterogeneity (ORgrade III vs. I 3.14; 95%CI 1.47-6.70 and ORgrade III vs. I 2.28; 95%CI 1.26-4.14, respectively). There were no associations between intratumoral heterogeneity and age, race or menopausal status. Conclusions: Intratumoral heterogeneity may account for a portion of the well-documented inter-laboratory discordance in ER and PR status, with implications for tumor subtype classification. Intratumoral heterogeneity was more prevalent in high grade tumors, indicating that it may be a feature of aggressive breast cancer. Furthermore, obese postmenopausal women were more likely to have intratumoral ER heterogeneity, suggesting a potential mechanism underlying the association between obesity and worse breast cancer prognosis. Although these data do not support an association between intratumoral heterogeneity and race, given that both high grade disease and obesity are more common in African Americans, future studies should explore a possible role for intratumoral heterogeneity in breast cancer racial disparities. Citation Format: Emma H. Allott, Joseph Geradts, Xuezheng Sun, Stephanie M. Cohen, Thaer Khoury, Wiam Bshara, Gary Zirpoli, Julie R. Palmer, Christine B. Ambrosone, Andrew F. Olshan, Melissa A. Troester. Intratumoral hormone receptor heterogeneity is a characteristic of high-grade breast cancer and is associated with inter-laboratory hormone receptor status discordance. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B21.

92 Background: Estrogen receptor (ER), progesterone receptor (PgR), and HER2 status are important biological markers for making decisions about breast cancer treatments. Although changes of hormone receptor (HR) and HER2 status with recurrence of breast cancer are clinically experienced, the frequency of discordance and clinical significance are still unknown. Thus, we investigated ER, PgR, and HER2 status with primary tumors and recurrent lesions, and assessed discordance rates and prognosis. Methods: We retrospectively identified recurrent breast cancer patients who had biopsies or resections of recurrent lesions between January 2007 to April 2012 at Keio University Hospital. HR status was assessed by immunohistochemistry (IHC) and determined using the Allred score. HR status was defined as positive when score was 3 and more. HER2 status was assessed by IHC and fluorescence in situ hybridization (FISH) analysis. We defined HER2 positivity as 3+ staining intensity by IHC or the presence of HER2 gene amplification by FISH. Results: Among 32 recurrences, 40% (13) were loco-regional recurrences (LLR) and 60% (19) were distant metastases (DM) (lung 14; liver 3; brain 1; pleura 1). Discordance rates in ER, PgR and HER2 status between the primary tumors and the recurrence lesions were 12.5%, 31.3%, and 13.8%, respectively. The most common change was loss of PgR. Changings from negative to positive in ER, PgR and HER2 status were found in 6.3%, 3.1%, and 3.4% of the patients, respectively. All gains were found in distant metastases. Discordance in ER and HER2 were more common in DM (15.8% and 17.6%) comparing with LRR (7.7% and 8.3%). Loss of HR status was not associated with a shorter time to progression (TTP) (ER: 19.3 vs. 8.5 months, p=0.185; PgR: 4.4 vs. 11.5 months, p=0.907). Patients with discordant HER2 status had significantly shorter TTP than with concordant status (0.9 vs. 11.5 months, p=0.012). Conclusions: Discordance of biological markers between primary and recurrent breast cancers were seen in 10-30%. Although HR discordance was not associated with prognosis, patients with HER2 discordance had poorer TTP. Tissue confirmation should be considered for making effective treatment decisions in recurrent breast cancer.

Accurate determination of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2) status was very important in selecting breast cancer treatment. Discordance of ER, PR, and HER2 status between core needle biopsy (CNB) and open excision biopsy (OEB) varied among reported studies. We performed a meta-analysis to compare the accuracy of CNB with that of OEB for ER, PgR, and HER2 status detection in breast cancer. Medical subject heading (MeSH) terms (Breast Neoplasm) and key words (biopsy OR mammotome) AND (incision OR excision OR surgery) AND (estrogen OR progesterone OR HER2 OR hormone). Patients with HER2 immunohistochemical 3+ or fluorescence in situ hybridization positive were classified into HER2[b] group. A total of 27 studies were eligible in this study. Aggregate positive ER and PgR rate was 80.0 and 69.5% for CNB; and 77.7 and 66.2% for OEB, respectively. The HER2 positive rate difference between CNB and OEB was only 0.2%. The pooled sensitivity of evaluating ER, PgR, and HER2 status in CNB compared with OEB was 0.970, 0.911, and 0.799 (0.813 for HER2[b]), respectively. All of AUC values for these status determination were larger than 0.9. Heterogeneity between studies was introduced by various factors in PgR and HER2[b] analysis. Subgroup analysis showed that the specificity and OR of CNB in studies with ER positive rate >78% was lower than studies with ER positive rate ≤78% (P < 0.05). This meta-analysis indicated that CNB had high diagnostic accuracy in evaluating ER, PgR, and HER2 status compared with OBE in breast cancer patients. In terms of 2-3% positive rate difference, ER and PgR status should be detected both on CNB and OEB samples, especially to retest their expression on CNB in patients with hormonal receptor negative tumors in OEB.

Hormone receptor status affects locoregional control in HER2‐positive breast cancer treated with trastuzumab

The aim of this study was to analyze the association between the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) in breast cancer with neoadjuvant therapy by using tissue biopsy and surgical specimens. This study included 78 patients with breast cancer, who presented to our hospital between June 1999 and June 2011, and were treated with neoadjuvant therapy and subsequent mastectomy or partial mastectomy. All clinicopathological data regarding pre-neoadjuvant biopsy and definitive surgical specimens were reviewed for accuracy. The status of ER, PR, and HER2 was determined by immunohistochemistry. Paired samples from 78 women (mean age 51.4 ± 11.7 years) were successfully analyzed. A switch in the status of ER was identified in 16 patients (20 %); PR, in 18 (23 %); and HER2, in 27 (35 %). There were no significant differences in the status of ER, PR, and HER2 between the primary tumor and the resected tumor after neoadjuvant therapy. Neoadjuvant therapy does not significantly influence the status of the steroid hormone receptors and the HER2 level in our study. Initial biopsy may be reliable for determining the appropriate adjuvant therapy, but final pathology are still needed to evaluate the prognosis and provided the alternative treatment when tumor recurrence. Further prospective study is needed to optimize the care available for breast cancer patients.

Receptor status (ER, PgR and HER2) discordance between primary tumor and locoregional recurrence in breast cancer

BackgroundWe investigated the reliability of core needle biopsy (CNB) in evaluating the status of hormone receptor (HR), human epidermal growth factor receptor (HER)-2, and Ki-67 status, and the effect of neoadjuvant chemotherapy (NAC) on the expression of these immunohistochemical markers.MethodsAmong 177 patients with breast adenocarcinoma, 95 patients underwent NAC and the remaining 82 patients made up the control group. Immunohistochemistry (IHC) was used to evaluate the expression status of estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67 in the specimens obtained by surgical excision or CNB.ResultsIn the control group, the expression of ER, PR, HER-2, and Ki-67 was highly consistent between samples from surgical excision or CNB (all r > 0.8, P < 0.05). In the NAC group, the proportions of samples with changes in ER, PR, HER-2, and Ki-67 expression were 12.7%, 24.1%, 5.1%, and 38.0%, respectively; the figures in the control group were 2.4%, 4.9%, 2.4%, and 7.3%, respectively, which significantly differed in ER, PR, and Ki-67 (P < 0.05), but not HER-2 (P > 0.05). In the NAC group, pre- and post-treatment ER+ rates did not significantly differ (P > 0.05), although PR+ and high Ki-67 expression rates did significantly differ (P < 0.05).ConclusionNeither CNB nor surgical excision samples gave highly consistent results in HR, HER-2, and Ki-67 status. NAC can alter HR and Ki-67 status in breast adenocarcinoma patients. NAC decreased PR+ rate and Ki-67 expression. The mean ER+ rate exhibited a decreasing, but insignificant trend after NAC treatment. NAC had no significant effect on HER-2 expression.

BackgroundThe 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.MethodsThe 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.ResultsThe 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).ConclusionsChanges 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.

158 Background: In female breast cancer, estrogen receptor (ER) and/or progesterone receptor (PR) positivity confers a favorable prognosis; however, the effect of these hormone receptors (HR) on survival in male breast cancer (MBC) is controversial. The aim of this study isto determine if there is a difference in the 5 year cancer specific survival (CSS) rate of patients in different HR subgroups of MBC using the SEER database. Methods: We included patients with MBC ≥ 18 years of age in the SEER database from 1990 to 2011. Patients with unknown or borderline ER or PR status were excluded. Patients were divided into four subgroups based on HR status: ER+/PR+, ER+/PR-, ER-/PR+, ER-/PR-. Univariate analysis was done using t-test and chi-square. Multivariate Cox regression analysis was used to evaluate hazard ratios and determine the significance of covariates. Kaplan -Meier method was used to estimate survival. Results: We included 3,341 patients. The mean age was 64.9 years (SD 12.7) and most (2736, 81.9%) were Caucasians. The majority (2770, 82.9%) had ER+/PR+ tumors, 377 (11.3%) had ER+/PR- , 33 (1.0 %) had ER-/PR+ and 161(4.8%) had ER-/PR- tumors. Caucasians were more likely to have MBC positive for both ER and PR compared to African-Americans (84.1% versus 74.3%, P&lt; 0.001). ER-/PR- tumors were more likely to be poorly differentiated compared to ER+/PR+ , ER+/PR- and ER-/PR+ (62.7%, 32.2%, 44.8%, 36.4% respectively , P&lt;0.001). There was a significant difference in 5 year CSS of HR subgroups only in stage III and IV, with subgroups positive for ER consistently showing improved survival compared to ER-/PR- (Table). On multivariate analysis, positive ER or PR status was independently associated with decreased hazard of death (Hazard Ratio: 0.68 (p = 0.03); 0.78 (p = 0.04) respectively). Conclusions: Our study showed a significant difference in the 5 year CSS rate of patients in different HR subgroups of advanced stages (III and IV) of MBC. Positive HR status was associated with a better prognosis. [Table: see text]