Quantitative Progesterone Receptor Expression and Efficacy of Anti‐estrogen Therapy in Breast Cancer

The central role of estrogen receptor (ER) presence in predicting which breast cancer patients are likely to benefit from anti‐estrogen therapies is well‐established, but the added benefit of progesterone receptor (PR) and in particular low levels of PR is less well understood. The objective of this study was to determine the quantitative relationship between borderline levels of PR and subsequent benefit from anti‐estrogen therapy. We examined data from 447 patients, age 50 or older. ER and PR levels were quantitated by conventional ligand binding assay and Scatchard plot analysis or by enzyme‐linked immunoassay. Comparison of clinical outcome in relation with ER and PR status was calculated using Kaplan‐Meier actuarial survival analysis and the log‐rank test. Subpopulation treatment effect pattern plot (STEPP) analysis was used to explore the interaction between treatment effects and ER or PR levels for the 409 patients with ER values greater than 0. For anti‐estrogen treated patients, when the ER and PR positivity cut‐off was set at 1.0 fmole/mg protein, there was a statistically significant advantage for patients with ER+PR+ over ER+ PR? tumors for both breast cancer‐free interval (BCFI) and overall survival (OS). STEPP analysis found no overall interaction between treatment outcome (5 year survival probability) and levels of hormone receptor. However, patients with borderline PR levels did not appear to benefit from anti‐estrogen therapy. PR levels above borderline in addition to the presence of ER predicts an increased probability of benefit from anti‐estrogen therapy in breast cancer patients.     

A multifactorial analysis of steroid hormone receptors in stages I and II breast cancer.

It has been shown that the level of estrogen receptors (ER), and to some extent progesterone receptors (PR), correlate to a high degree to the response to endocrine therapy in advanced breast cancer patients. To evaluate the prognostic value of ER/PR in early breast cancer, 80 patients with stages I and II were studied. They all underwent modified radical mastectomy. Patients with stage I disease (negative LN) received no further treatment, while those with stage II received standard adjuvant chemotherapy. All the patients were followed for 4 years. The ER and PR were measured in each primary tumor by the glycerol density gradient method. Values of 10 fmole/mgm protein or greater were considered positive (+) and less than 10 fmole/mgm were considered negative (-). The results revealed: (1) Fifty-two patients (65%) had ER+, of which 44 (85%) were also PR+; 28 patients had ER-, of which 24 were also PR- (p less than 0.0001). (2) ER/PR correlated with age as 71% of the patients over age 50 had ER+/PR+, compared to 33% of those under age 50 (p less than 0.05). (3) Postmenopausal patients had a higher incidence of ER+/PR+. (4) Primary tumors less than 2 cm in size had higher ER+; 71% in those with stage I and 80% in stage II. (5) Fifty-eight per cent (38) of patients with ductal carcinoma had ER+/PR+, compared to 67% (4) with lobular carcinoma. (6) The disease-free survival of patients with ER+ tumors was significantly longer than those with ER- tumors (p less than 0.005) both in positive and negative LN patients. The same was true for PR+ compared to PR- (p less than 0.005), but only in those with stage II disease. The overall survival rates were similarly significant in favor of ER+ and PR+ patients (p less than 0.025), but only in stage II disease. It seems that the status of steroid hormone receptors has a major prognostic factor second only to the LN status.     

Primary therapy with ECF in combination with a GnRH analog in premenopausal women with hormone receptor-positive T2-T4 breast cancer

Patients with hormone receptor-positive tumors less often show a pathological complete response (pCR) than do those with hormone receptor-negative tumors. The addition of endocrine therapies may improve the clinical benefits of primary therapies in these patients. We investigated the efficacy of the epirubicin+cisplatin+fluorouracil (ECF) as continuous infusion) regimen in association with a gonadotropin-releasing hormone (GnRH) analog in 36 premenopausal women with T2-T4a-d N0-2 M0 ER and/or PgR-positive breast cancer. Median age was 39.5 years (range 26-53). Clinical response (complete or partial) was observed in 27 out of 36 patients (75% 95% CI 57.8-87.9%) and a pCR was observed in four patients (11%). Nine (25%) patients had stable disease and no progression was observed. Twenty-one patients (58%) were submitted for breast-conserving surgery and 15 had a radical mastectomy. No baseline clinical and biological characteristics significantly correlated with response. Thirty out of 31 patients evaluable for endocrine assessment had documented ovarian suppression, which occurred after a median of 28 days (range 20-43). We conclude that the combination of ECF and a GnRH analog is associated with a high response rate in the primary treatment of breast cancer. Further studies combining chemotherapy and endocrine agents are warranted in patients with hormone receptor-positive tumors.     

Disease burden and treatment outcomes in second-line therapy of patients with estrogen receptor-positive (ER+) advanced breast cancer: A review of the literature

ObjectiveTo determine the variable burden of disease of patients with advanced estrogen receptor-positive (ER+) breast cancer and assess the current treatment landscape after failure of first-line endocrine therapy.MethodsA comprehensive literature review was performed (2000–2011) by searching Medline via PubMed, and Embase and Cochrane databases, to assess disease burden (i.e. societal, humanistic, and/or economic burden) and treatment landscape for second-line therapy of ER+ advanced breast cancer in postmenopausal women.ResultsOnly 1 study was identified that evaluated burden of disease based on ER status (ER+, ER-negative, or ER-unknown); this study was a subgroup analysis assessing the impact of breast cancer recurrence over 10 years. The investigators reported that only minor differences in survival and medical costs were noted based on ER status in relapsing patients. Regardless of ER status, patients with breast cancer recurrence consumed more healthcare resources and were associated with more costly care than those without recurrence. A total of 7 studies were identified related to treatment outcomes of second-line therapy in ER+ patients. A combined international population totaled >3800 patients who had progressed on prior hormonal therapy, including tamoxifen and aromatase inhibitors. Three trials performed a comparative efficacy/safety assessment of an ER antagonist vs. aromatase inhibitor, 1 trial compared an aromatase inhibitor to megestrol acetate, and 1 trial compared 2 aromatase inhibitors. Among each of the studies evaluated, no significant differences were observed in the primary efficacy endpoint, and the safety profiles were similar. Two additional studies demonstrated a similar or better efficacy and safety profile based on different dosing evaluations.ConclusionsCurrently, there is insufficient evidence on the economic and humanistic burden associated with ER status, and this gap warrants further research. With increasing drug resistance and greater economic burden associated with breast cancer recurrence, there is an unmet medical need for improved treatment in this patient population.     

The role of ovarian ablation in the management of breast cancer

Abstract: In recent years the role of ovarian ablation as a therapeutic modality not only in the prevention but also in the treatment of breast cancer has reemerged after its initial use more than a century ago. BRCA‐1 and BRCA‐2 mutation carriers have an 85% lifetime risk of developing breast cancer. Bilateral salpingo‐oophorectomy is effective in reducing the risk of developing breast cancer in both BRCA‐1 and BRCA‐2 mutation carriers by 50%. Tamoxifen reduces the risk of breast cancer in BRCA‐2 mutation carriers, but not in BRCA‐1 mutation carriers. Breast cancer arising in BRCA‐1 mutation carriers is often estrogen receptor (ER) negative, unlike breast cancer developing in BRCA‐2 mutation carriers. Sixty percent of premenopausal patients with breast cancer have ER‐positive disease and 25% of breast cancer patients are premenopausal at diagnosis. The Early Breast Cancer Trialists’ Collaborative Group review has shown ovarian ablation to be an effective adjuvant therapy for premenopausal breast cancer patients less than 50 years of age. But the Early Breast Cancer Trialists’ overview also shows the benefit of ovarian ablation is uncertain if these patients also receive chemotherapy. Does the overview underestimate the efficacy of ovarian ablation? Some patients in these trials were ER negative. Most women less than 50 years of age who receive adjuvant chemotherapy become menopausal. So there is a need to test ovarian function suppression in the group who can benefit, or in other words, those that remain premenopausal after chemotherapy and have endocrine responsive breast cancer.     

Impact of Oncotype DX on Treatment Decisions in ER‐Positive,Node‐Negative Breast Cancer with Histologic Correlation

Oncotype DX, a gene‐expression profiling assay, provides stratification of patients with estrogen‐receptor positive, lymph‐node‐negative early breast cancer into risk groups based on recurrence score, which are associated with distant recurrence and response to chemotherapy. This study aims to determine whether Oncotype DX influences clinicians' treatment decisions, and whether assay results correlate with histologic assessment. Fifty patients with estrogen‐receptor positive, node‐negative early breast cancer analyzed by Oncotype DX and operated on by two breast surgeons were included. To assess effect on treatment decisions, clinical vignettes were created by retrospective chart review. Physicians were then presented with the clinical vignettes and instructed to make a treatment decisions (i.e., hormone therapy alone versus hormone therapy combined with chemotherapy) both before and after knowledge of the recurrence score. To assess correlation with histologic assessment, a prospective, blinded review of tumor slides was performed by two pathologists. Based on this review, tumors were placed into low, intermediate and high risk groups for comparison with Oncotype DX assay results. Treatment decisions were changed based on Oncotype DX results in 36 and 18% of cases by breast surgeons and medical oncologists, respectively. All tumors categorized as high risk by Oncotype DX were categorized as high risk based on histologic assessment, and 96% of cases categorized as low risk by recurrence score were categorized as low or intermediate risk by histologic assessment. Oncotype DX significantly influences management of estrogen‐receptor positive, lymph‐node‐negative early breast cancer. Further studies are needed to assess association of histologic categorization to assay results.     

Triple‐Negative Breast Cancer in Ghanaian Women: The Korle Bu Teaching Hospital Experience

Breast cancers that have negative or extremely low expression of estrogen receptor and progesterone receptor and non‐amplification of human epidermal growth factor receptor‐2 (HER2)/neu are termed triple‐negative breast cancer (TNBC). The majority of TNBC tumors belong to the biologically aggressive basal subtype, and they cannot be managed with targeted endocrine or anti‐HER2/neu agents. In western, high resource environments, risk factors for TNBC include younger age at diagnosis and hereditary susceptibility. Women of African ancestry in the United States and in continental Africa have higher frequencies of TNBC, prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer survival disparities related to racial/ethnic identity. Efforts to document and confirm the breast cancer burden of continental Africa have been hampered by the limited availability of registry and immunohistochemistry resources. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa, and to compare the frequencies as well as risk factors for TNBC versus non‐TNBC in this large referral tertiary hospital. The Korle Bu Teaching Hospital is affiliated with the University of Ghana and is located in Accra, the capital of Ghana. We conducted an institutional, Department of Pathology‐based review of the breast cancer cases seen at this facility for the 2010 calendar year, and for which histopathologic specimens were available. The overall study population of 223 breast cancer cases had a median age of 52.4 years, and most had palpable tumors larger than 5 cm in diameter. More than half were TNBC (130; 58.3%). We observed similar age‐specific frequencies, distribution of stage at diagnosis and tumor grade among cases of TNBC compared to cases of non‐TNBC. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively younger age at diagnosis compared to Caucasian Americans and African Americans. The triple‐negative molecular marker pattern was the most common subtype of breast cancer seen among this sample of Ghanaian women, regardless of age, tumor grade, or stage of diagnosis. Research into the molecular pathogenesis of TNBC may help elucidate the reasons for its increased prevalence among women with African ancestry.     

Influence of estrogen receptors on survival and recurrence in patients with breast cancer without lymph node metastases

A retrospective chart review was conducted to determine the prognostic effect of estrogen receptor (ER) protein in patients with node-negative operable breast cancer. One hundred nine patients with breast cancer whose tumors underwent ER analysis and whose lymph node negativity was established histologically were studied. Based on life-table analysis, the overall survival at six years was 92.7% for ER-positive patients, 95.3% for ER-negative patients, and 94.4% for ER-borderline patients. The disease-free survival was 83.3%, 92.8%, and 71.4%, respectively. Survival and disease-free survival were also correlated to menopausal status. The difference in survival was not statistically significant at six years. We conclude that in node-negative primary operable breast cancer, ER status should not be used as a discriminant for adjuvant treatment.     

Breast Cancer Subtypes as Defined by the Estrogen Receptor (ER), Progesterone Receptor (PR), and the Human Epidermal Growth Factor Receptor 2 (HER2) among Women with Invasive Breast Cancer in California, 1999–2004

Abstract: Breast cancer research examining either molecular profiles or biomarker subtypes has focused on the estrogen receptor negative/progesterone receptor negative/human epidermal growth factor receptor 2 negative (ER−/PR−/HER2−) and ER−/PR−/HER2+ subtypes. Less is known about the epidemiology or clinical outcome of the other subtypes. This study examines the eight combinations of ER/PR/HER2 in patients with invasive breast cancer. The 5‐year relative survival and the distribution among demographic, socioeconomic, and tumor characteristics of each of the subtypes are examined. Using the California Cancer Registry, 61,309 women with primary invasive breast cancer were classified according to ER/PR/HER2 status. Five‐year relative survival was computed for the eight subtypes. Bivariate analyses were used to assess the distribution of cases across all subtypes. Multivariate logistic regression was used to compute the adjusted odds of having one of the five subtypes with the best and worst survival. Survival varied from 96% (ER+/PR+/HER2−) to 76% (ER−/PR−/HER2+ and ER−/PR−/HER2−). The four subtypes with the poorest survival were all ER negative. Women who were younger than age 50, non‐Hispanic black or Hispanic, of the lowest SES groups, and had stage IV tumors that were undifferentiated were overrepresented in ER−/PR−/HER2+ and triple negative (ER−/PR−/HER2−) subtypes. Asian Pacific Islanders had increased odds (OR = 1.41; 95% confidence interval [CI] = 1.26–1.57) of having the ER−/PR−/HER2+ subtype. Stage III tumors (OR = 1.25; 95% CI = 1.08–1.44) and stage IV tumors (OR = 1.58; 95% CI = 1.27–1.98) had higher odds than stage I tumors of being ER−/PR−/HER2+. Stage IV tumors (OR = 0.54; 95% CI = 0.44–0.67) strongly decreased the odds of the ER−/PR−/HER2− subtype. Poorly differentiated and undifferentiated tumors were over 20 times as likely as well‐differentiated tumors of being ER−/PR−/HER2− or ER−/PR−/HER2+. There are considerable differences in survival, demographics, and tumor characteristics among the eight subtypes. We recommend reporting breast cancer as an ER/PR/HER2 subtype and precisely documenting demographic and tumor characteristics.     

Renal cancer steroid receptors: biochemical basis for endocrine therapy.

Estradiol receptor (ER) and progesterone receptor (PR), found in experimental renal cancer as well as in normal human kidney and in human renal cell carcinoma (RCC), have been measured in 27 RCCs from patients submitted to surgery and endocrine therapy in an attempt to predict the response to progestational therapy. Of these 27 tumors 59% were positive for ER and 59% for PR; 37% were positive and 19% negative for both ER and PR. The follow-up of 23 patients showed that progestational therapy, started in 18 patients, has given favorable results in 14 patients and negative results in 3 patients with ER-PR- renal cancer. Antiestrogenic therapy, started soon after nephrectomy in 1 patient with ER+PR- renal cancer and lung metastases, failed since the patient died 8 months after surgery.     

The Loss of Estrogen and Progesterone Receptor Gene Expression in Human Breast Cancer

Hormone responsiveness is a critical determinantof breast cancer progression and management, and theresponse to endocrine therapy is highly correlated withthe estrogen receptor (ER)³ and progesterone receptor (PR) status of tumor cells. Thus, keyareas of study in breast cancer are those mechanismsthat regulate ER and PR expression in normal andmalignant breast tissues. One-third of all breastcancers lack ER and PR; these conditions are associatedwith less differentiated tumors and poorer clinicaloutcome. In addition, approximately one-half ofER-positive tumors lack PR protein and patients withthis phenotype are less likely to respond tohormonal therapies than those whose tumors express bothreceptors. Since PR is induced by ER; its presence is amarker of a functional ER. In this review, we will discuss possible mechanisms for loss of ER andPR gene expression, especially structural changes withineach gene including deletions, polymorphisms ormethylation. Improved understanding of the pathways that lead to loss of ER and/or PR proteinsshould allow the development of better predictiveindicators as well as novel therapeutic approaches totarget these hormone-independent cancers.     

Correlation of estrophilin content of primary mammary cancer to eventual endocrine treatment.

The estrogen receptor protein content of recurrent breast cancer correlates well with the clinical response of hormonal manipulation. This predictive value of the ER of the primary tumor obtained at the time of mastectomy has not yet been proven. If this predictive capability should hold for primary tumors and eventual endocrine treatment, the ramifications are obvious: endocrine therapy could be offered to patients on a rational basis and adjuvant therapy could be considered on a plausible biochemical basis. This report details our observations as to the ER content of the primary tumor and the eventual result of endocrine therapy. Thirty-seven patients whose tumor ER was determined from the primary tumor eventually underwent some form of endocrine therapy for recurrent disease. Fifteen of the primary tumors had significant ER content and 22 possessed insignificant amounts. Only one of the 22 patients with insignificant ER content was benefited by endocrine treatment. Those patients whose tumors contained low amounts of ER experienced recurrence of their disease more rapidly than did those with higher ER content. There was no correlation of age, cell type of tumor or metastatic site with the ER content of the tumor. There is a positive correlation between response to chemotherapy and ER content of tumor. Measurement of the estrogen receptor protein content of the primary breast tumor is a reliable method for choosing patients for eventual endocrine therapy. Those patients whose tumors contain insignificant estrophilin are not candidates for such attempts at palliation.     

Renal cancer steroid receptors: biochemical basis for endocrine therapy.

The hypothesis of hormone dependence of human renal cancer, based on experimental and clinical data, has recently been supported by estradiol-receptor (ER) and progesterone-receptor (PR) studies. ER and PR, found in experimental renal cancer as well as in normal human kidney and in human renal cell carcinoma (RCC), have been measured in 27 RCCs from patients submitted to surgery and endocrine therapy, in an attempt to predict the response to progestational therapy . Of these 27 tumors, 59% were positive for ER and 59% for PR; 37% were positive and 19% were negative for both ER and PR. The follow-up of 23 patients so far investigated showed that progestational therapy, commenced in 18 patients, has given favorable results in 14 patients and negative results in 3 patients with ER-PR- renal cancer. Antiestrogenic therapy, started after nephrectomy in 1 patient with ER+PR- renal cancer and lung metastases, failed since the patient died 8 months after surgery.     

70岁以上女性乳腺癌临床病理特征及预后分析

目的:分析70岁以上女性乳腺癌患者的临床病理特征、治疗方式及预后影响因素。方法:回顾2007年1月—2010年12月哈尔滨医科大学附属肿瘤医院乳腺外科接诊并接受手术治疗的203例70岁以上老年女性乳腺癌患者的临床资料,分析其临床病理特点及生存情况。结果:203例患者中,临床TNMⅠ期患者67例(33.0%),Ⅱ期患者117例(57.6%);无腋窝淋巴结转移患者92例(53.5%);浸润性导管癌166例(81.8%),为主要病理类型;177例行免疫组织化学检查,ER、PR阳性与HER-2过表达患者分别为123例(69.5%)、114例(64.4%)、23例(13.0%);乳腺癌改良根治术153例(75.4%),为主要手术方式;术后接受内分泌治疗患者111例(54.7%),化疗患者28例(13.8%)。单因素分析显示年龄、淋巴结状态、ER、PR、组织学分级与内分泌治疗与患者总生存时间(OS)有关,淋巴结状态、ER、PR、HER-2、内分泌治疗与化疗与患者无病生存时间(DFS)有关(均P0.05);COX多因素分析显示年龄、淋巴结状态和PR为OS的独立影响因素,淋巴结状态为DFS的独立影响因素(均P0.05)。结论:老年女性乳腺癌具有独特生物学特性,主要治疗方式为手术治疗。年龄、淋巴结状态和PR是老年女性乳腺癌的独立预后因素。     

Proportion of estrogen or progesterone receptor expressing cells in breast cancers and response to endocrine therapy

Immunohistochemical determination of ER/PR status has been the gold standard in clinical practice of breast cancer for decades. A cut-off of ‘1%’ is commonly used; however, this is not supported by strict evidence. How the proportion of ER/PR-positive cells influences the response to endocrine therapy has been scarcely reported, either. To address these issues, 486 and 663 invasive breast cancer cases treated with or without adjuvant tamoxifen respectively (median follow-up period, 12.8 years) were enrolled, and effect of tamoxifen treatment was compared among ER/PR-positive or -negative groups immunohistochemically determined using various cut-offs. Tamoxifen significantly improved 5 years disease-free survival in ER/PR-positive, but not in ER/PR-negative, cases even using immunohistochemical >0% cut-off. Cases with ≥67% ER/PR expressing cells responded to tamoxifen by far the best. Patients having tumors without any ER/PR-positive cells should be excluded from endocrine therapy, whereas this therapy should be strongly recommended for those with ≥67% ER/PR-positive cells.     

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.     

Role of endocrine responsiveness and HER2/neu overexpression in inflammatory breast cancer treated with multimodality preoperative therapy

We analyzed the role of endocrine responsiveness and HER2/neu overexpression in inflammatory breast cancer treated with multimodality preoperative therapy. Thirty-eight patients (estrogen receptor [ER] and/or progesterone receptor [PgR] >or=10% of the cells 21, premenopausal 14, Ki-67 expression >or=20% of the cells 30, HER2/neu overexpressed 11) were treated with six courses of epirubicin, cisplatin and fluorouracil (FU) as continuous infusion, perioperative FU as continuous infusion, mastectomy and loco-regional radiotherapy. In endocrine-responsive patients, endocrine treatment (letrozole, either alone or if premenopausal with triptorelin) was given preoperatively and as adjuvant treatment. There were 32 objective responders (84.2%; 95% CI 70.0-94.6%), three of whom had pathologic complete remission. At the multivariate analysis disease-free survival was significantly worse in patients with ER and PgR absent tumors compared with the positive expression cohort (hazards ratio [HR]: 5.91; 95% CI 1.69-20.7; p = 0.005), in particular if HER2/neu overexpression was detected (HR: 16.5; 95% CI 4.24-64.5; p < 0.0001). New multimodality and targeted strategies should be explored in endocrine nonresponsive breast cancer.     

Special issues related to the adjuvant therapy in very young women

A small minority of breast cancer patients consists of young women (<40 years: <6%). Thus, they may not be properly represented in clinical trials. They present with unfavorable tumor characteristics, but young age is an independent negative prognosticator: age is a surrogate for biological mechanisms determining an aggressive cancer phenotype. In premenopausal patients with estrogen receptor-positive (ER+) tumors, adjuvant ovarian function suppression (OSF) was as effective as chemotherapy in ten randomized clinical trials. Chemotherapy reduces the risks of recurrence and death irrespective of endocrine responsiveness of the tumor; however, in patients with ER+ tumors this might result in chemotherapy-induced menopause. Accordingly, OFS did not prolong survival in addition to chemotherapy in meta-analyses and recent clinical trials except in subgroups of particularly young women. Adjuvant tamoxifen is efficient in premenopausal patients with ER+ tumors irrespective of age and the use of chemotherapy. Clinical trials addressing the role of OFS are underway, and future trials should be planned so that the population of young women can be properly analyzed.     

Aromatase inhibitors as solely treatment in postmenopausal breast cancer patients

Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy, although the incidence of local recurrences was higher. Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery. We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases, refuse surgery or are of old age. Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery, were judged ineligible for surgery because of comorbidity, or were of old age were treated with endocrine therapy using aromatase inhibitors only. Digital mammography and high-end breast ultrasound were used to assess tumor sizes. The mean age of the patients was 74 years (range 52-102 years). All patients suffered from breast cancer. The mean follow-up interval was 40 months (range 5-92 months). Seven patients (12%) achieved complete clinical remission, 31 (57%) partial response giving an overall objective response rate of 69%. In addition, seven (12%) patients showed stable disease, giving a clinical benefit rate (complete remission + partial response + stable disease rate) of 81%. Eleven patients (19%) progressed after an initial partial response or stable disease. Only one patient (2%) progressed on endocrine therapy within the first months. Eventually, 22 (39%) patients underwent surgery after informed consent to achieve better local tumor control. Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery, who are judged ineligible for surgery, or are of old age.     

Preoperative concurrent chemo- and endocrine therapies for women with large operable breast cancer expressing steroid hormone receptors

Preoperative chemotherapy and endocrine therapy yielded low pathological complete remission (pCR) rates in patients with endocrine responsive breast cancer. Patients with large operable (cT2–T3, N0–2, M0), ER ≥10% breast cancer were treated in two consecutive studies with preoperative chemotherapy (Study I: six courses of either fluorouracil, leucovorin, vinorelbine (FLN), or vinorelbine, cisplatin, and continuous infusion of fluorouracil (ViFuP), at the discretion of the treating physician; Study II: capecitabine and oral vinorelbine (CAVINO)). Concurrent letrozole (in association with triptorelin if premenopause) was given. Sixty-five (58 evaluable) and 55 (all evaluable) patients were enrolled in the two studies. In Study I there were 43 objective responders (74%, 95% CI 63–85%), three of whom had pCR. Thirty-nine objective responses (91%) and all pCR were observed in patients with tumors expressing ER ≥50%. In Study II 34 patients (62%, 95% CI 49–75%) had an objective response. Endocrine therapy administered together with new intravenous, containing regimens should be explored in the preoperative treatment of endocrine responsive breast cancer.