Progesterone Receptor Status Significantly Improves Outcome Prediction Over Estrogen Receptor Status Alone for Adjuvant Endocrine Therapy in Two Large Breast Cancer Databases

2003 ◽  
Vol 21 (10) ◽  
pp. 1973-1979 ◽  
Author(s):  
Valerie-Jeanne Bardou ◽  
Grazia Arpino ◽  
Richard M. Elledge ◽  
C. Kent Osborne ◽  
Gary M. Clark
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Endocrine Therapy ◽  
Multivariate Analyses ◽  
Adjuvant Endocrine Therapy ◽  
Endocrine Treatment ◽  
Receptor Status ◽  
Risk Of Death ◽  
Er Positive

Purpose: To determine whether progesterone receptor (PgR) status provides additional value to estrogen receptor (ER) status and improves prediction of benefit from endocrine treatment among patients with primary breast cancer. Patients and Methods: Clinical outcomes of patients in two large databases were analyzed as a function of steroid receptor status. The first database (PP), contained 3,739 patients who did not receive any systemic adjuvant therapy and 1,688 patients who received adjuvant endocrine therapy but no chemotherapy. The second database (SPORE), contained 10,444 patients who received adjuvant endocrine therapy but no chemotherapy. Biochemical ER and PgR assays were identically performed in two different central laboratories. Results: In univariate and multivariate analyses, the prognostic significance of PgR status among systemically untreated patients is modest. Among endocrine-treated patients, however, multivariate analyses, including lymph-node involvement, tumor size, and age, demonstrate that PgR status is independently associated with disease-free and overall survival. For recurrence, the reduction in relative risk (RR) was 25% for ER-positive/PgR-negative patients and 53% for ER-positive/PgR-positive patients, compared with ER-negative/PgR-negative patients (P < .0001, PP patients). Patients with ER-positive/PgR-negative tumors have a reduction in RR of death of 30% (SPORE patients) and 38% (PP patients), compared with patients with ER-negative/PgR-negative tumors (P < .0001). For ER-positive/PgR-positive tumors, the reduction of the risk of death was greater than 46% in SPORE patients and 58% in PP patients, indicating that ER-positive/PgR-positive patients derive more benefit from endocrine therapy (P < .0001). Conclusion: When accurately measured, PgR status is an independent predictive factor for benefit from adjuvant endocrine therapy. Therefore, PgR status should be taken into account when discussing RR reductions expected from endocrine treatment with individual patients.

Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in estrogen receptor-positive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21160-e21160
Author(s):  
Ji sun Kim ◽  
Wonshik Han ◽  
Jee Man You ◽  
Hee-Chul Shin ◽  
Soo Kyung Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Breast Density ◽  
Adjuvant Endocrine Therapy ◽  
Absolute Difference ◽  
Mammographic Breast Density ◽  
Short Term ◽  
Er Positive ◽  
Positive Breast Cancer

e21160 Background: Previous studies showed that anti-estrogen therapy lowers mammographic breast density (MD). We hypothesized that the short-term change of breast density can be a surrogate marker predicting response to adjuvant endocrine therapy (ET) for breast cancer. Methods: We analyzed data of 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET including tamoxifen and aromatase inhibitor. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction was defined as an absolute difference between the MD of two mammography images: taken preoperatively and 8-20months after the start of adjuvant ET.. Results: After median follow up of 68.8 months, overall recurrence rate was 7.5% (80/1065). Mean MD reduction was 5.9% (-17.2 to 36.9). In a logistic regression analysis, age<50, high preoperative MD, and longer interval between start of ET to the 2nd mammogram were significantly associated with higher MD reduction (p value<0.05). In a survival analysis using Cox model, tumor size (>2cm), lymph node positive, high Ki-67 (≥10%), and lower MD reduction were independent factors significantly associated with recurrence-free survival (p<0.05). The hazard of recurrence increased proportionally according to the less degree of MD reduction. Conclusions: MD change during short-term use of adjuvant ET was a significant predictive factor for long-term recurrence in ER-positive breast cancer. It is urgent to develop effective treatment strategy in patients who have less MD reduction in spite of about 1 year of ET.

scholarly journals The impact of tumor progesterone receptor status on optimal adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer

Cancer ◽  
2006 ◽  
Vol 106 (12) ◽  
pp. 2576-2582 ◽  
Author(s):  
Rinaa S. Punglia ◽  
Karen M. Kuntz ◽  
Eric P. Winer ◽  
Jane C. Weeks ◽  
Harold J. Burstein
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Adjuvant Endocrine Therapy ◽  
Early Stage Breast Cancer ◽  
Progesterone Receptor Status ◽  
Receptor Status ◽  
The Impact

scholarly journals Long-Term Follow-Up of the Intergroup Exemestane Study

2017 ◽  
Vol 35 (22) ◽  
pp. 2507-2514 ◽  
Author(s):  
James P. Morden ◽  
Isabel Alvarez ◽  
Gianfilippo Bertelli ◽  
Alan S. Coates ◽  
Robert Coleman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Estrogen Receptor Status ◽  
Adjuvant Endocrine Therapy ◽  
Absolute Difference ◽  
Receptor Status ◽  
Estrogen Receptor Positive ◽  
The Absolute

Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy. Given the large number of non–breast cancer–related deaths now reported, breast cancer–free survival (BCFS), with censorship of intercurrent deaths, was the primary survival end point of interest. Analyses focus on patients with estrogen receptor-positive or unknown tumors (n = 4,599). Results At the time of the data snapshot, median follow-up was 120 months. In the population that was estrogen receptor positive or had unknown estrogen receptor status, 1,111 BCFS events were observed with 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group. The data corresponded to an absolute difference (between exemestane and tamoxifen) at 10 years of 4.0% (95% CI, 1.2% to 6.7%), and the hazard ratio (HR) of 0.81 (95% CI, 0.72 to 0.92) favored exemestane. This difference remained in multivariable analysis that was adjusted for nodal status, prior use of hormone replacement therapy, and prior chemotherapy (HR, 0.80; 95% CI, 0.71 to 0.90; P < .001). A modest improvement in overall survival was seen with exemestane; the absolute difference (between exemestane and tamoxifen) at 10 years in the population that was estrogen receptor positive or had unknown estrogen receptor status was 2.1% (95% CI, −0.5% to 4.6%), and the HR was 0.89 (95% CI, 0.78 to 1.01; P = .08). For the intention-to-treat population, the absolute difference was 1.6% (95% CI, −0.9% to 4.1%); the HR was 0.91 (95% CI, 0.80 to 1.03, P = .15). No statistically significant difference was observed in the proportion of patients who reported a fracture event in the post-treatment period. Conclusion The Intergroup Exemestane Study and contemporaneous studies have established that a strategy of switching to an aromatase inhibitor after 2 to 3 years of tamoxifen can lead to sustained benefits in terms of reduction of disease recurrence and breast cancer mortality.

Endocrine Treatment of Breast Cancer: Current Perspectives, Future Directions

2017 ◽  
Vol 8 (03) ◽  
Author(s):  
Tazia Irfan ◽  
Mainul Haque ◽  
Sayeeda Rahman ◽  
Russell Kabir ◽  
Nuzhat Rahman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Premenopausal Women ◽  
New Drugs ◽  
Effective Control ◽  
Endocrine Treatment ◽  
Estrogen Production ◽  
Hormone Sensitive

Breast cancer remains one of the major causes of death in women, and endocrine treatment is currently one of the mainstay of treatment in patients with estrogen receptor positive breast cancer. Endocrine therapy either slows down or stops the growth of hormone-sensitive tumors by blocking the body’s capability to yield hormones or by interfering with hormone action. In this paper, we intended to review various approaches of endocrine treatments for breast cancer highlighting successes and limitations. There are three settings where endocrine treatment of breast cancer can be used: neoadjuvant, adjuvant, or metastatic. Several strategies have also been developed to treat hormone-sensitive breast cancer which include ovarian ablation, blocking estrogen production, and stopping estrogen effects. Selective estrogen-receptor modulators (SERMs) (e.g. tamoxifen and raloxifene), aromatase inhibitors (AIs) (e.g. anastrozole, letrozole and exemestane), gonadotropin-releasing hormone agonists (GnRH) (e.g. goserelin), and selective estrogen receptor downregulators (SERDs) (e.g. fulvestrant) are currently used drugs to treat breast cancer. Tamoxifen is probably the first targeted therapy widely used in breast cancer treatment which is considered to be very effective as first line endocrine treatment in previously untreated patients and also can be used after other endocrine therapy and chemotherapy. AIs inhibit the action of enzyme aromatase which ultimately decrease the production of estrogen to stimulate the growth of ER+ breast cancer cells. GnRH agonists suppress ovarian function, inducing artificial menopause in premenopausal women. Endocrine treatments are cheap, well-tolerated and have a fixed single daily dose for all ages, heights and weights of patients. Endocrine treatments are not nearly as toxic as chemotherapy and frequent hospitalization can be avoided. New drugs in preliminary trials demonstrated the potential for improvement of the efficacy of endocrine therapy including overcoming resistance. However, the overall goals for breast cancer including endocrine therapy should focus on effective control of cancer, design personalized medical therapeutic approach, increase survival time and quality of life, and improve supportive and palliative care for end-stage disease.

Male Versus Female Breast Cancers

2003 ◽  
Vol 127 (1) ◽  
pp. 36-41 ◽  
Author(s):  
D. Muir ◽  
R. Kanthan ◽  
S. C. Kanthan
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Male Breast Cancer ◽  
Male Breast ◽  
High Grade ◽  
Breast Cancers ◽  
Receptor Status ◽  
Female Breast ◽  
Grade 3

Abstract Context.—The rate of male breast cancer is a small fraction of that observed in females, thus severely limiting our understanding of the pathogenesis of this condition. It remains unclear whether the biological behavior and tumor progression associated with male breast cancer parallel that of the female form. Objectives.—To evaluate the immunohistochemical profile of male breast carcinomas and to compare this profile with that of stage-matched female breast cancers. Design.—Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Foundation over a period of 26 years (1970–1996). Fifty-nine of these cases had formalin-fixed, paraffin-embedded tissue blocks available for the purposes of this study. All cases were reviewed and a standardized modified Bloom-Richardson grading criterion was applied. Estrogen receptor status, progesterone receptor status, c-Erb-B2 expression, p53 expression, and Bcl-2 expression were evaluated by immunohistochemistry. Results from 240 consecutive cases of stage-matched female breast cancers analyzed in the same laboratory were used as a standard set for comparison. Results.—Male breast cancers tended to be high grade (85% grade 3) in comparison with the female breast cancers (50% grade 3). In descriptive analysis across all stages of disease, male carcinomas were more frequently estrogen receptor positive (81% vs 69%) than their female counterparts. Despite their high grade, they were less likely to overexpress p53 (9% vs 28%) and Erb-B2 (5% vs 17%) than the female counterparts. There was no significant difference in either progesterone receptor (63% vs 56%) or Bcl-2 (79% vs 76%) overexpression. Stratified analysis by stage-matched controls showed no statistically significant differences among the men and women with stage I disease. However, in stage II–matched samples, statistically significant differences were observed between the 2 groups. The male cancers were more likely to overexpress estrogen receptor (81.6% vs 64.4%, P = .04), progesterone receptor (71.1% vs 47.5%, P = .01), and Bcl-2 (78.9% vs 69.4%, P = .20). They also showed statistically significant lower expression of p53 (7.9% vs 36.3%, P = .001) and Erb-B2 (5.3% vs 23.8% P = .01). Conclusion.—Male breast cancers display distinct immunophenotypic differences from those occurring in women, implying a different pathogenesis in the evolution and progression of this disease. Such differences may play key roles in therapeutic management, warranting different treatment strategies in comparison to female breast cancers.

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