Prognostic and predictive value of TFF1 for adjuvant endocrine therapy in Chinese women with early ER positive breast cancer: Comparing aromatase inhibitors with tamoxifen

Factors that predict in favor of an aromatase inhibitors (AIs) over tamoxifen (TAM) in estrogen receptor (ER) breast cancer remains to be identified. We compared progesterone receptor (PR) and trefoil factor 1 (TTF1) status (+ve versus −ve) as predictive of superior effect of AI’s over tamoxifen among a total of 1973 Chinese women with early ER+ breast cancer. The expression of TFF1 was independently associated with ER and PR. However, there was no correlation with TFF1 and HER-2 expression. Treatment effect was more pronounced in the ER+/TFF1+ postmenopausal patients with a hazard ratio favoring AIs (HR = 0.397, 95%CI 0.183-0.860), but not in the PR positive cohorts (HR = 0.466, 95%CI 0.186-1.164). We suggested that AIs was better than TAM especially in the postmenopausal patients with ER+/TFF1+ breast cancer; however the clinical application of this observation still requires further prospective studies.     

Evaluation of the pathologic and prognostic correlates of estrogen receptors in primary breast cancer.

The presence of estrogen receptors in breast cancer tissue has been reported to correlate with improved prognosis in women after mastectomy. The prognostic value (if any) of the presence or absence of estrogen receptors (ER) in malignant breast tissue was evaluated 104 women who were treated for primary breast cancer, whose pathology was re-examined, and whose records were subjected to multifactorial analysis. Sixty patients were ER positive, and 44 were ER negative, and a total of 94 who had curative resections were available for follow-up (mean follow-up time 20 months). The presence of estrogen receptors showed significant positive correlations with age, lobular cancer, and a variant of infiltrating duct cancer that is prevalent in the elderly and characterized by the presence of cells showing granular eosinophilic cytoplasm. Of 26 cases identified as infiltrating duct cancer showing granular eosinophilic cytoplasm, 22 were ER positive, one was ER negative, and three had borderline values. There was no significant difference between the groups with regard to family history of breast cancer or hysterectomy. A striking observation was noted in the ER positive group in which there were seven cases of second primary breast cancers, whereas no such cases occurred in the ER negative patients (p=0.05). There was a higher percentage of nodal metastases in the patients who were ER positive compared with those who were ER negative; 27 of 53 (51%) of the ER positive patients has positive nodes compared with four of 40 (32%) who were ER negative, p = 0.08. There was no significant correlation of disease free survival nor time to recurrence in either the overall group nor according to stage. In patients whose tumors had been reviewed and graded, there was no prognostic relationship of ER status in high grade tumors, but in patients with low-grade tumors, improved disease-free survival was demonstrated in patients who were ER negative. Although the estrogen receptor assay is a highly useful tumor marker and guide for therapy of advanced breast cancer, its relationship to the prognostic variables of primary breast cancer is complex and controversial and merits continued study.     

A comparison of prognostic tumor markers obtained on image-guided breast biopsies and final surgical specimens

BACKGROUND: This study was initiated to determine whether tumor markers obtained on image-guided breast biopsy specimens provide accurate prognostic information for women with invasive breast cancer. METHODS: Prognostic tumor markers on preoperative image-guided biopsy and final surgical specimens were compared in 44 patients with invasive breast cancer. RESULTS: Progesterone receptor (PR) discordance was 18%. In 87% of PR discordant cases, the image-guided biopsy was positive and the final specimen was negative (P = 0.03). Tumor grade was discordant in 36% of patients Discordance for estrogen receptor (ER) = 2%; MIB-1 = 18%; Her2/neu = 9%; EGFR = 10%; p53 = 9%; and bcl-2 = 0%. The discordance for these markers was random and did not reach statistical significance. CONCLUSION: Image-guided core needle biopsies provide reliable information for the majority of prognostic tumor makers. A positive progesterone receptor is significantly more likely to be determined by core biopsy rather than the final surgical specimen. Tumor grade should be based upon the final surgical specimen whenever possible.     

The androgen receptor as a surrogate marker for molecular apocrine breast cancer subtyping

The Androgen Receptor (AR) is a potential prognostic marker and therapeutic target in breast cancer. We evaluated AR protein expression in high-risk breast cancer treated in the adjuvant setting. Tumors were subtyped into luminal (ER+/PgR±/AR±), molecular apocrine (MAC, [ER−/PgR−/AR+]) and hormone receptor negative carcinomas (HR-negative, [ER−/PgR−/AR−]). Subtyping was evaluated with respect to prognosis and to taxane therapy. High histologic grade (p < 0.001) and increased proliferation (p = 0.001) more often appeared in MAC and HR-negative than in luminal tumors. Patients with MAC had outcome comparable to the luminal group, while patients with HR-negative disease had increased risk for relapse and death. MAC outcome was favorable upon taxane-containing treatment; this remained significant upon multivariate analysis for overall survival (HR 0.31, 95%CI 0.13–0.74, interaction p = 0.035) and as a trend for time to relapse (p = 0.15). In conclusion, AR-related subtyping of breast cancer may be prognostic and serve for selecting optimal treatment combinations.     

Clinical Significance of Biological Markers at Primary Operation for Metastatic Breast Cancer

Purpose: To identify the prognostic value of biological markers at initial operation for metastatic breast cancer, we measured the presence of estrogen receptor-alpha (ERα), progesterone receptor (PgR) and human epidermal growth factor receptor type 2 (HER2),and histological grade (HG) of tumors. Methods: One-hundred and seventy-six patients, aged 29 to 90 (median: 51 years), with recurrent breast cancer underwent primary operation at our department during the period from 1983 to 2000. Clinicopathological factors examined at primary operation included menopausal symptoms, presence of axillary lymph node metastasis, tumor size, HG, HER2, ERα and PgR.Factors examined at recurrence included site of primary recurrence, disease-free interval(DFI) and tumor markers, such as CEA and CA15-3. The relationship between these factors and prognosis following recurrence was assessed. Results: Menopausal status, axillary lymph node metastasis and tumor size at primary operation had no significant effect on prognosis. Patients with low HG, positive expession of ERα and PgR, and low HER2 expression had a good prognosis, similar to those with long DFI and distant metastases. After distant metastases, HER2 was found to be the most important prognostic factor following recurrence and in predicting response to drug therapy.Conclusion: Biological factors indicating tumor malignancy at the time of the first operation are also important prognostic factors following tumor recurrence.     

Prognostic Value of Breast Cancer Subtypes,Ki‐67 Proliferation Index,Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.     

Tubular Carcinoma of the Breast: Immunohistochemical and DNA Flow Cytometric Profile

▪ Abstract: Molecular markers of ordinary invasive ductal carcinoma of the breast have been extensively studied and their prognostic significance has been assessed. A common variant of breast cancer, tubular carcinoma, has an excellent prognosis as judged from several clinicopathologic studies. One would assume that tubular carcinomas have "favorable" molecular markers, however, published series of tubular carcinomas do not include molecular markers. We describe the molecular markers of 39 consecutive tubular carcinomas collected between January 1995 and July 1997. DNA ploidy, S-phase, estrogen and progesterone receptor (ER and PR, respectively) expression, and immunoreactivity for MIB-1, p53, and erbB2 were evaluated. Seventy-two percent of tubular carcinomas were DNA diploid, 49% had an S-phase less than 5%, 95% were ER positive, 69% were PR positive, 88% had less than 10% MIB-1-positive cells, 97% were p53 negative, and 97% did not overexpress erbB2 protein. Thus tubular carcinomas exhibit favorable molecular characteristics, which may play a role in their good prognosis. ▪     

Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

BackgroundThis meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR).MethodsA systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521).ResultsA total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50–4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95%CI, 1.93–6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67–4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03–14.1, P = 0.78).ConclusionsIncreased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.     

Prognostic potential of topoisomerase IIα and HER2 in a retrospective analysis of early advanced breast cancer patients treated with adjuvant anthracycline chemotherapy

Background

After surgery and anthracycline adjuvant treatment, about 60% of early advanced breast cancer patients develop recurrence. These differences in treatment outcome indicate the need to identify markers for risk of recurrence. The aim of this study was the retrospective analysis of relationship between tumour features (topoisomerase II?? (TOPOII??), human epidermal growth factor receptor 2 (HER2), hormone receptors, cytokeratin (CK)5/6 expression and proliferation rate) and disease-free survival (DFS) of breast cancer patients treated with anthracyclines in adjuvant setting.

Material and methods

The study was performed in the group of 172 patients (mean age: 52.8 years, T1-T2, N1-N2, M0). HER2, TOPOII??, estrogen receptor (ER) and progesterone receptor (PgR) expression and proliferation rate were studied immunohistochemically. HER2 overexpression was confirmed by fluorescence in situ hybridisation (FISH). These data were correlated with 5-year DFS.

Results

In univariate analysis, lower TOPOII?? expression (median value ≤ 11.9%) and tumour grade G1 + G2 were favourable prognostic factors. All tumours were classified into four subtypes: (1) lower TOPOII?? expression and G1 + G2, (2) lower TOPOII?? expression and G3, (3) higher TOPOII?? expression and G3, and (4) higher TOPOII?? expression and G1 + G2. In Cox multivariate regression analysis, tumour subtype distinguished by TOPOII?? expression and grade was independent prognostic factor for DFS. All patients (n = 52) with TOPOII?? lower expression and G1 + G2 tumours, survived 5 years without any evidence of disease.

Conclusion

The results suggest that lower TOPOII?? expression and lower tumour grade are favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline chemotherapy.     

The prognostic significance of single hormone receptor positive metastatic breast cancer: An analysis of three randomised phase III trials of aromatase inhibitors

We analysed the outcomes of women with metastatic breast cancer (MBC) from three randomised phase III trials of aromatase inhibitors according to oestrogen receptor (ER) and progesterone receptor (PgR) status. Both receptors were analysed in 1010 of the 1870 women (54%), including 31 that were ER-/PgR-, which were excluded. Of the remaining 979, 726 (74%) were ER+/PgR+ but 253 were single hormone receptor positive (213 ER+/PgR-, 40 ER-/PgR+). Although there were no differences in clinical benefit or time to progression, the median overall survival of women with ER+/PgR+ tumours was significantly longer than those with single HR positive tumours (800 versus 600 days, p = 0·01). In women with ER+ tumours, the median overall survival of those with tumours that were also PgR+ was significantly longer than those that were PgR- (800 versus 625 days, p = 0·02). The PgR status is an important prognostic factor for survival in MBC.     

ERΔE5在乳腺癌组织中的表达及临床意义探讨

目的：通过检测乳腺癌和癌旁乳腺组织（乳腺癌标本边缘外5cm）中雌激素受体α（Estrogen Receptor,ERα）剪切变异体ERΔE5表达水平的差异,探讨ERΔE5在乳腺癌组织中的表达及临床意义。方法：培养乳腺癌细胞株ZR-75-1,采用RT-PCR检测目的基因ERΔE5,建立阳性对照体系。以液氮冷冻储存的59例乳腺癌组织和59例癌旁乳腺组织提取目的基因,进行对照实验,检测ERΔE5在乳腺癌组织和癌旁乳腺组织中的表达状况,分析二者的表达差异及其临床意义。结果：在ER阳性乳腺癌标本中,ERΔE5阳性20例（20/44）,ER阴性的乳腺癌标本中,ERΔE5阳性6例（6/15）,两者差异无统计学意义（P=0.7170）;在人表皮生长因子受体2（human epidermal growth factor receptor,HER-2）阳性的乳腺癌标本中,ERΔE5阳性20例（20/22）,HER-2阴性的乳腺癌标本中,ERΔE5阳性6例（6/37）。采用单因素分析,发现乳腺癌标本中ERΔE5的阳性表达与HER-2的阳性表达呈正相关（P〈0.0001）。在乳腺癌标本中ERΔE5的阳性表达率为44.07%（26/59）;在癌旁乳腺组织中未见ERΔE5的表达,两者比较差异有统计学意义（P〈0.0001）。在乳腺癌标本中ERΔE5的表达与临床分期无相关性（P=0.9084）。结论：在乳腺癌标本中ERΔE5的表达显著高于癌旁乳腺组织,而且与HER-2表达呈正相关,提示ERΔE5可能是一种新的临床预后的指标。     

乳腺癌组织中HER2、ERα、ERβ、PR的表达及其相关性分析

目的探讨雌激素受体α（ERα）、雌激素受体β（ERβ）、孕激素受体（PR）、人类表皮生长因子受体2（HER2）在乳腺癌组织中的表达及其与TNM分期和腋窝淋巴结状况的关系。方法随机选择我院在2004年12月至2007年12月收治的HER2高表达（＋＋＋）51例与无表达（-）53例乳腺浸润性导管癌病例，分别检测乳腺癌组织的ERα、ERβ、PR的表达水平，分析其与TNM分期、腋窝淋巴结转移等临床指标的相关性。结果104例乳腺癌患者，TNM分期为I期的占14．42％，Ⅱ期占62．50％，Ⅲ期占19．23％，Ⅳ期占3．85％；HER2阳性的淋巴结转移率为41．18％，HER2阴性的转移率为47．5％；ERα、ERβ、PR的阳性表达率分别为52．88％、63．46％、73．08％。ERβ与ERα、PR的表达呈正相关（P〈0．01），与HER2的表达负相关（P〈0．01）；ERα与PR的表达正相关（P〈0．01），与HER2负相关（P〈0．01），PR与HER2的表达负相关（P〈0．05）；ERα、ERβ、PR、HER2的表达与淋巴结转移情况及TNM分期无显著相关性。结论HER2作为乳腺癌预后不良的重要指标与作为乳腺癌预后良好的重要指标ERα、ERβ、PR的表达呈负相关，与TNM分期及腋窝淋巴结转移状态未显示明显相关性。     

Is the TNM Staging System for Breast Cancer Still Relevant in the Era of Biomarkers and Emerging Personalized Medicine for Breast Cancer – An Institution's 10‐year Experience

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).     

Prognostic Significance of the Combination of Biological Parameters in Breast Cancer

To evaluate whether the combination of biological parameters increases their prognostic value, the expression of epidermal growth factor receptor (EGFR), DNA ploidy, and estrogen receptor (ER) status were analyzed on 998 patients with breast cancer. Poor findings for each biological parameter were positive for EGFR, aneuploid for DNA ploidy, and negative for ER. According to the number of poor findings in these three parameters, the groups with none (309 cases), one (377 cases), two (161 cases), and three (151 cases) poor findings were classified. A significant ( P < 0.0001) difference was found in the disease-free survival (DFS) among the four groups. A multivariate analysis indicated the combination of three biological parameters to be an independently significant factor for DFS, while the relative risk gradually increased as the number of poor findings increased. In conclusion, the present study indicated a gradual increase in the prognostic significance as the number of combined biological parameters increased.     

Topoisomerase II-�� as a predictive factor of response to therapy with anthracyclines in locally advanced breast cancer

Background

Topoisomerase II-?? is a molecular target of anthracyclines; several studies have suggested that topoisomerase II-?? expression is related to response to anthracycline treatment. The objective of this study was to evaluate if topoisomerase II-?? overexpression predicts response to anthracycline treatment in locally advanced breast cancer patients.

Material and methods

Topoisomerase II-??, HER2, estrogen receptor (ER) and progesterone receptor (PR) expression were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded breast tumors from 111 patients presenting with locally advanced breast cancer between 1995 and 2002. The prognostic value of these markers was analyzed using a multivariate proportional hazards regression model and an interaction analysis between topoisomerase II-?? status and dose intensity.

Results

Tumors from 40 patients (36%) showed topoisomerase II-?? overexpression, 62 patients (56%) for ER, 39 (35%) for PR and 26 (23%) for HER2. There were no significant correlations between topoisomerase II-?? expression and response to therapy, progression-free survival (PFS) or overall survival (OS). Anthracycline dose intensity had a significant impact on PFS and OS in patients overexpressing topoisomerase II-?? (P = 0.010 and 0.027, respectively). Negative PR (P = 0.041), positive HER2 (P = 0.013) were identified as risk factors in the multivariate model. The multivariate analysis in patients topoisomerase II-?? negative shown no significance (HR = 0.92, IC 95% 0.39-2.15, P = 0.839) while the multivariate analysis in topoisomerase II-?? positive, dose intensity shown to be statistically significant (HR = 2.725, IC 95% 1.07-6.95, P = 0.036).

Conclusions

Our data do not support a correlation between topoisomerase II-?? expression in breast cancer patients and improved clinical benefit with anthracycline therapy. However, they do suggest that tumors overexpressing topoisomerase II-?? may experience better clinical benefit with higher anthracycline dose intensity.     

Disease-Free Survival and Prognostic Significance of Metastatic Lymph Node Ratio in T1-T2 N Positive Breast Cancer Patients. A Population Registry-Based Study in a European Country

Background  The ratio of positive lymph nodes between the total number of harvested lymph nodes (metastatic lymph node ratio, MLNR) has been proposed as an alternative to the total number of lymph nodes alone in predicting outcomes for patients with breast cancer. Because there can be differences between European and non-European populations, the authors present the first study analyzing MLNR influence over disease-free survival (DFS) by using a population-based cancer registry in a European country. Methods  Data from 441 patients with T1-2 N1-3 breast cancer included in the Castellon Cancer Registry (Comunidad Valenciana, Spain) were used. Cumulative DFS was determined using the Kaplan-Meier method, with univariate comparisons between groups through the log-rank test. The Cox proportional hazards model was used for multivariate analysis. Results  At univariate analysis, factors influencing the 10-year DFS rate were tumor size, conservative or nonconservative surgery, histologic grade, histologic type, radiotherapy, tamoxifen, estrogen and progesterone receptor status, p53 status, total number of positive lymph nodes, and MLNR. At multivariate analysis, tumor size, MLNR, and progesterone receptor status were revealed to be independent prognostic factors; the metastatic lymph node ratio was the most notably independent factor (hazard ratio 1.02, 5.21, and 0.61, respectively). Conclusions  MLNR is a stronger prognostic factor for recurrence than the total number of positive lymph nodes in T1-T2 N1-3 breast cancer.     

Diagnosis and Management of Male Breast Cancer

Background  Male breast cancer (MBC) is rare with an incidence of 1% of all breast cancers. The evidence about the treatment is derived from the data on the management of the female breast cancer because conduction of randomized, controlled trials is impossible due to the rarity of the disease. In this study, we review the special features, overall management, diagnosis, and treatment of patients with MBC managed under our care with a brief review of the current literature. Methods  During the period 1998 to 2006, we managed 1103 new patients with breast cancer in St Mary’s Hospital. Among these, 14 patients were men. We retrospectively reviewed the case notes, histology, and follow-up notes of all the newly diagnosed patients with MBC. Results  In this series, 28.6% had only in situ disease. Moreover, in 78.6% there was an in situ component present. One patient was found to have a cancer on the microdochectomy specimen after an operation for single duct nipple discharge, and in a second patient the cancer was found in the gynecomastia operation specimen. All ten invasive tumors were estrogen receptor positive (ER +ve), whereas eight were progesterone receptor positive (PgR +ve). With a median follow-up of 35 months, there was one locoregional recurrence and one disease-associated death. Conclusions  In situ cancer may not be as rare as previously reported among patients with MBC. Increased patient awareness and early assessment by a specialist is a key to early diagnosis and improved outcomes.     

Estrogen and Progesterone Receptors in Benign Breast Epithelium

Abstract: Estrogen and progesterone are necessary for lobulo-alveolar development of the human breast, and there is an abundance of epidemiologic literature implicating estrogen and possibly progesterone exposure as promoters of breast malignancy. The investigation of estrogen receptor (ER) and progesterone receptor (PgR) distribution in normal and benign breast tissue may be a measure of susceptibility of the tissue to these hormones. Earlier data from radioligand binding assays showed that benign breast tissue expressed little or no ER; newer immunohistochemical (IHC) methods have led to the investigation of benign breast tissue from at least 1243 women in 12 studies in the last 9 years. These show that the level of expression of ER and PgR in normal breast epithelium is significantly lower than in receptor positive carcinomas. Immunostaining patterns for both receptors show a great deal of heterogeneity. There is general agreement that stromal and myoepithelial cells are negative for both ER and PgR. A growing body of evidence suggests that PgR is the dominant sex steroid receptor in the normal breast. Mean values for PgR positive cells in breast epithelium range from 24% to 29%; ER is positive by IHC in 3% to 15.6% of normal breast epithelial cells. No firm conclusions are possible as yet regarding overexpression in proliferative epithelium. There is agreement that the proportion of ER positive cells declines in the second half of the menstrual cycle, but there is no clear cut relationship between PgR positivity with the menstrual cycle. Oral contraceptive use appears to decrease the proportion of ER positive cells, and increase mammary epithelial proliferation. A recent case-control analysis of epithelial ER and PgR status reports an association of ER positive benign epithelium with the presence of cancer in the breast. Future research should include a systematic quantitative analysis of receptor expression in epithelial proliferative lesions, and the longitudinal follow-up of women who have had receptor testing on benign breast tissue.     

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer.MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status.Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression.ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.