Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy. METHODS: PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC. RESULTS: Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary. CONCLUSIONS: Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.

The effect of neoadjuvant platinum-based chemotherapy in BRCA mutated triple negative breast cancers -systematic review and meta-analysis.

BACKGROUND: Triple negative breast cancers (TNBC) are associated with an aggressive clinical course, earlier recurrence and short survival. BRCA - mutated tumours represent up to 25% of all TNBC. BRCA status is being studied as a predictive biomarker of response to platinum agents. However, the predictive role of BRCA status is still uncertain in this setting. Since TNBC is a very heterogeneous group of diseases, it is important to identify subsets of TNBC patients that may benefit from platinum-based therapy. This study aims to establish if the presence of a germline BRCA mutation in women with TNBC improves the pathologic complete response (pCR) after neoadjuvant chemotherapy with platinum compounds. METHODS: An extensive literature search was performed in MEDLINE, EMBASE and LILACS databases, WHO (WHO International Clinical Trials Registry Platform) and the Cochrane Controlled Trials Register Database, for online trial registries and conference proceedings. The measurement of pCR was assessed by pathology review of breast specimen and lymph nodes. RESULTS: The overall OR was computed using random effects models.Seven studies were included, comprising a total of 808 TNBC patients, among which 159 were BRCA mutated. Among mutated TNBC patients, 93 (93/159; 58.4%) achieved pCR, while 410 wildtype patients (410/808; 50.7%) showed pCR (OR 1.459 CI 95% [0.953-2.34] p = 0.082) although this result did not reach statistical significance. CONCLUSIONS: This meta-analysis shows that the addition of platinum to chemotherapy regimens in the neoadjuvant setting increases pCR rate in BRCA - mutated as compared to wild-type TNBC patients. However, this trend did not achieve statistical significance. TRIAL REGISTRATION: CRD42018092341.

Factors associated with ovarian function recovery after chemotherapy for breast cancer: a systematic review and meta-analysis.

STUDY QUESTION: Which factors related to patient, treatment or disease are associated with ovarian function recovery after chemotherapy in premenopausal women with breast cancer? SUMMARY ANSWER: Younger age and GnRH agonist (GnRHa) administration during chemotherapy were significantly associated with menses recovery, but this recovery was less likely in patients exposed to taxanes. WHAT IS ALREADY KNOWN: To date, published meta-analyses have only assessed GnRHa administration as a possible factor for ovarian function recovery, and their results were conflicting. Current guidelines present distinct recommendations regarding the use of GnRHa for fertility preservation (FP) in women with breast cancer. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of published studies in the English, Portuguese, French or Spanish languages (1990-2015), ongoing trials or completed trials (1990-2015) and conference proceedings (2000-2015) were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched the MEDLINE, Embase, LILACS, Scielo, Toxline and DART databases, online trial registries and conference proceedings. Studies were eligible if they included premenopausal women with early breast cancer treated with chemotherapy, reported ovarian function recovery data and identified factor(s) associated with recovery. Two authors independently screened the studies, extracted data and assessed the risk of bias. An odds ratio (OR) was estimated from the number of recovery events. A meta-analysis was conducted using a random-effects model. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen articles were included. Five different factors were analysed: younger age and baseline levels of anti-Müllerian hormone (patient-related factors), co-administration of GnRHa, addition of taxanes to anthracycline-based chemotherapy and addition of endocrine therapy to chemotherapy (treatment-related factors). Menses recovery was the most used marker. Younger age (≤40 years) and exposure to GnRHa were positively associated with menses recovery (OR 6.07 and 2.03, respectively) but exposure to taxanes adversely affected recovery (OR 0.49). Significant heterogeneity among studies was found. LIMITATIONS, REASONS FOR CAUTION: A general limitation of the included studies is the use of menses as the main recovery marker. Regarding GnRHa, the substantial heterogeneity and conflicting results limit the interpretation of our results. Studies that use additional markers and have a longer follow-up are needed. WIDER IMPLICATIONS OF THE FINDINGS: The decision for using chemotherapy regimens with taxanes must take into account their potential adverse effects on female fertility. Considering the conflicting results regarding GnRHa agonist use, other fertility preservation strategies should also be considered. STUDY FUNDING/COMPETING INTERESTS: No external funding was received. There are no conflicts of interest to declare. PROSPERO REGISTRATION NUMBER: This review was registered at PROSPERO (CRD42015013494).

A case of endometrial stromal sarcoma with synchronous bilateral adenocarcinoma of ovary.

Endometrial stromal tumor is a rare mesenchymal uterine tumor. We report the case of a patient with endometrial stromal sarcoma and concomitant bilateral endometrioid adenocarcinoma of the ovary in the context of pelvic endometriosis. The patient underwent a complete cytoreduction including total hysterectomy and bilateral adnexectomy, pelvic lymphadenectomy, appendicectomy, infracolic omentectomy, and pelvic peritonectomy. This is the first report to our knowledge that describes a synchronous endometrial stromal sarcoma and bilateral endometrioid adenocarcinoma of the ovary.