Preoperative chemotherapy and endocrine therapy in patients with breast cancer (original) (raw)
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Current Status of Neoadjuvant Endocrine Therapy in Early Stage Breast Cancer
Current treatment options in oncology, 2018
Neoadjuvant endocrine therapy (NET) with Ki67-based response monitoring is a practical, cost-effective approach to the management of clinical stage II and III estrogen receptor-positive (ER+) breast cancer. In addition to marked improvements in rates of breast conservation, the identification of extreme responders on the basis of the preoperative endocrine prognostic index (PEPI) provides a rationale to avoid chemotherapy on the basis of highly favorable prognosis in some patients. Finally, samples accrued from patients treated with neoadjuvant therapy are providing valuable insights into the molecular basis for intrinsic resistance to endocrine therapy and promise a more rational basis and precise approach to the systemic treatment of ER+ breast cancer.
The Breast, 2007
Neoadjuvant endocrine therapy (NAET) can expand the number of breast cancer patients who can be treated with breast-conserving surgery and can predict benefit from adjuvant endocrine therapy. Because no validated surrogate markers for long-term outcome have been established, we conducted prospective trials to evaluate pathological response and Ki-67 index following treatment with tamoxifen or anastrozole. The study population included postmenopausal women with operable breast tumors that were both estrogen and progesterone receptor-positive and larger than 3 cm. Response was classified as pathological response (minimal response or better) and non-response. Non-responding (25.5%, vs. response 85.9%, p ¼ 0.002), axillary node-positive (58.4% vs. node negative 100%, p ¼ 0.045), and high pretreatment Ki-67 index (41.4% vs. low Ki-67 87.1%, p ¼ 0.03) patients were significantly associated with poor 5-year relapse-free survival. Multivariate analysis of relapse-free survival indicated that pathological response was independent. Therefore, pathological response may be a favorable prognostic factor after NAET.
Cancer Research Journal
Introduction and objective: There is discrepancy in practice worldwide whether testing molecular profile on residual carcinoma is warranted and if treatment options should be modified according to final molecular profile of tumor. Therefore, the current study was conducted to evaluate potential changes in breast biomarkers; estrogen receptor, progesterone receptor, HER-2 and Ki67 expression before and after neoadjuvant chemotherapy in Egyptian patients with breast cancer. Patients and method: a hundred locally advanced (initial clinical stage IIB-IIIC) breast carcinoma patients were treated by one of two protocols of neoadjuvant chemotherapy. First protocol: 4 cycles of AC (adriamycin, cyclophosamide) repeated every 21 days, followed by 12 weeks of paclitaxel. Second protocol: FAC (fluorouracil, adriamycin, cyclophosamide) or FEC (fluorouracil, epirubicin, cyclophosamide) for 6 cycles to be repeated every 21 days. Immunohistochemisty of breast biomarkers were performed on both initial biopsies and also surgical resection specimens for each patient. Result: There was statistically significant change of ER (p=0.03). Fifty five tumors were initially negative and thirty nine became negative after neoadjuvant chemotherapy. The rate of conversion from negative to positive was 14%. Forty seven of tumors were initially negative progesterone receptors (PR) and sixty two became negative after neoadjuvant chemotherapy. PR status showed statistically significant change between before and after neoadjuvant chemotherapy (p=0.04). The rate of conversion of PR from positive to negative was 15%. There is no statistically significant change of HER-2 before and after neoadjuvant chemotherapy (p=0.98). There is statistically significant change from high to low Ki 67 index (p=0.006). Rate of conversion changes of Ki 67 from high to low was 20%. Conclusion: neoadjuvant chemotherapy change receptor status and reduce K i67 expression. This change in hormone receptor status from negative to positive offers new endocrine therapy to this group of patients. Accordingly, reevaluation of hormone receptors after neoadjuvant chemotherapy is required to guide further adjuvant treatment.
Predictive markers of endocrine response in breast cancer
World Journal of Experimental Medicine
Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor (ER) as the direct (for tamoxifen and fulvestrant) or indirect (for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant (pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogenregulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.
This study examined postmenopausal estrogen receptor-positive breast cancer patients who received prospective neoadjuvant endocrine therapy (NAET) with tamoxifen or anastrozole to determine if the 21gene recurrence score (RS) predicts NAET responses. RS scores were determined from pretreatment core biopsy specimens. Although half of the specimens yielded insufficient RNA, the remaining samples were highly representative. Patients with a low RS tended to respond better than those with an intermediate or high RS (n ¼ 43). Response rates by RS were similar between the tamoxifen and anastrozole groups. Patients with a low RS tended to have better relapse-free survival (RFS) than those with an intermediate or high RS (5y-RFS; 100% vs. 84% and 73%, respectively). These results suggest that RS predicts responses to NAET with tamoxifen or anastrozole. Because this pilot study examined a small sample size, these results should be validated in larger studies.
Breast Cancer, 2011
Aromatase inhibitors (AIs) were more effective than tamoxifen as a neoadjuvant endocrine therapy (NAE) for postmenopausal women with estrogen receptor (ER)positive breast cancer. Neoadjuvant AIs were shown to reduce tumor volume and to allow the performance of breast-conserving surgery (BCS) in cases that would normally require mastectomy. Predictive markers of neoadjuvant AIs may be ER-rich, progesterone receptor (PgR)rich and human epidermal growth factor receptor 2 (HER2)-negative tumors. However, the ability of HER2 expression to predict a response to neoadjuvant AIs is controversial. Pathological tumor size, nodal status, Ki67 level, and ER score are predictive for the survival of postmenopausal women with breast cancer who have been treated with NAE. These factors could be useful in order to select patients who do not require chemotherapy. Indeed, neoadjuvant AIs are a potential treatment option for postmenopausal women with ER-rich breast cancer who prefer BCS despite having large tumors suitable for mastectomy.
Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells. Analysing these changes has the potential to improve the prediction of which specific patients will respond to endocrine treatment. Serially profiled biopsies during treatment in the neoadjuvant setting offer promise for accurate and early prediction of response to both current and novel drugs and allow investigation of mechanisms of resistance. In addition, recent advances in monitoring tumour evolution through non-invasive (liquid) sampling of circulating tumour cells and cell-free tumour DNA may provide a method to detect resistant clones and allow implementation of personalized treatments for metastatic breast cancer patients. This review summarises current and future biomarkers and signatures for predicting response to endocrine treatment, and discusses the potential for using approved drugs and novel agents to improve outcomes. Increased prediction accuracy is likely to require sequential sampling, utilising preoperative or neoadjuvant treatment and/or liquid biopsies and an improved understanding of both the dynamics and heterogeneity of breast cancer.
Neoadjuvant endocrine therapy for breast cancer: past, present and future
Anti-Cancer Drugs, 2008
Neoadjuvant endocrine therapy studies for breast cancer are a great opportunity to develop insights into the biologic basis for the efficacy of estrogen receptor-targeting agents. Neoadjuvant endocrine treatment is also appealing from the drug development perspective. Theoretically, a promising new adjuvant endocrine strategy could be first tested as a short-term neoadjuvant treatment against a standard medication. Improvements in tumor response rate, surgical outcomes, and evidence for enhanced efficacy at the cellular level, for example in terms of the effect on proliferation, would provide a sound basis for taking the new approach forward into the resource-demanding setting of a phase III adjuvant trial. The potential of randomized phase III neoadjuvant endocrine treatment trials was first emphasized by the results of a double-blind study by Eiermann et al (Letrozole P024) 2 that compared 4 months of the aromatase inhibitor letrozole with tamoxifen as neoadjuvant treatment for women with hormone-receptor-positive tumors who were ineligible for breast-conserving surgery. Letrozole outperformed tamoxifen in terms of clinical and radiologic response rates as well as in the incidence of subsequent breast-conserving surgery. Interestingly, the advantage of letrozole appeared to be particularly evident in a subpopulation of tumors with estrogen-receptor-positive (ERϩ) and human epidermal growth factor receptor (HER) 1 and/or HER2-positive tumors, indicating that the comparison of endocrine agents in the neoadjuvant setting could provide insights into the molecular basis for differences in efficacy between endocrine agents. 3 The enhanced efficacy of letrozole was also apparent at the level of the cell cycle, since letrozole suppressed tumor Ki67 immunohistochemical staining to a greater extent than tamoxifen. 4 These results were consistent with the advantages of third generation aromatase inhibitors over tamoxifen in other disease settings. 5
Neoadjuvant Endocrine Therapy for Operable Breast Cancer: A Retrospective Analysis of Real-World Use
Journal of Nippon Medical School, 2021
Background: A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing the role of NET in breast cancer care. Methods: In a consecutive series of women with operable breast cancer who received NET for !28 days, associations of NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survival with clinicopathological factors were examined. Results: NET objectives were reduction in surgical extent in 49 patients, avoidance of surgery in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1,923), 869.8 (range, 36-4,859), and 55.8 (range, 39-113) days, respectively, in these cohorts (success rate: 79.6%, 64.5%, and 100%, respectively), and the differences were significant. Among patients in the former two cohorts, progression-free survival was significantly better in patients with stage 0 or I disease, ductal carcinoma in situ or invasive ductal carcinoma, !71% estrogen receptor (ER) positivity, and the surgical extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly associated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high preoperative endocrine prognostic index at the time of surgery after NET. Better recurrence-free survival after surgery was significantly associated with high ER expression after NET or high progesterone receptor expression before or after NET. Conclusions: NET can help reduce surgical extent or avoid surgery in women with early breast cancer, ductal carcinoma, or high ER expression. NET may also aid in decisions related to postoperative systemic therapy to improve survival.