Abstract: Endocrine treatment represents the cornerstone of endocrine-sensitive premenopausal early breast cancer. The estrogen blockade plays a leading role in the therapeutic management of hormone receptor-positive breast cancer together with surgery, radiotherapy, and selective antiestrogen treatments. For several years, selective estrogen receptor modulators, such as tamoxifen, have represented the mainstay of therapy. The role of amenorrhea has been extensively elucidated in the past year: the benefit observed with chemotherapy-induced amenorrhea has strengthened its therapeutic role. Luteinizing hormone-releasing hormone (LHRH) has been introduced in oncology practice to induce amenorrhea in order to increase the advantage obtained from endocrine treatment. Triptorelin is one of the most widely used LHRH analogs currently available in clinical practice. It was recently investigated in two major clinical trials that studied the role of complete estrogen blockade in the premenopausal setting. Both showed the clinical benefit due to ovarian suppression treatment, primarily in high-risk patients. Furthermore, triptorelin and other LHRH analogs have recently been investigated in the attempt to preserve the ovarian function in young patients. The medical treatment of early breast cancer is always evolving in the effort to search for safe and efficacious treatments. The role of LHRH analogs is actually well recognized as contributing to the improvement of the medical treatment of premenopausal women with early breast cancer. Keywords: adjuvant, hormone therapy, LHRH, amenorrhea
Myofibroblastoma of the breast is a rare benign stromal tumor that occurs in both sexes with a higher prevalence in male breast of older populations. Furthermore, myofibroblastoma can arise in extra mammary sites, along the milk-line. A variety of morphological variants in addition to the classic type have been identified. The differential diagnosis includes both benign and malignant entities that, through the use of clinical and radiological imaging, is difficult to characterize. Histopathological examination and immunohistochemistry are fundamental in the establishment of appropriate management of the disease and avoidance of overtreatment. The present study focuses on two cases of male mammary myofibroblastoma, with a short literature review.
Abstract Triple-negative breast cancer (TNBC) patients who do not obtain pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Risk factors for relapse in this subset of patients are poorly characterized. This study aimed to identify predictive factors for relapse in TNBC patients without pCR after NACT. Women with TNBC treated with NACT from January 2008 to May 2020 at the Modena Cancer Center were included in the analysis. We identified 142 patients with median follow-up of 55 months. After NACT, 62 patients obtained pCR (43.9%). Young age at diagnosis (< 50 years) and high ki-67 ( > 20%) were significantly associated to pCR. Lack of pCR after NACT resulted in worse 5-year EFS and OS. Factors independently predicting EFS in patients without pCR were the presence of multifocal disease (HR 3.22; 95% CI, 1.28–8.11; P 0.01) and Residual Cancer Burden (RCB) III (HR 3.8; 95% CI, 1.12–12; P 0.03). These data can be used to stratify patients and potentially guide treatment decision-making, identifying appropriate candidates for treatment intensification especially in neo/adjuvant setting.
Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades.
In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.
e13674 Background: BRCA germline (gBRCA) mutations occur in 11-15% of women with unselected ovarian cancers (OC), whereas somatic BRCA (sBRCA) mutations occur in approximately 5-7% of cases. The impact of sBRCA mutations on OC outcome is still debated. Methods: With the aim to explore the prognostic role of sBRCA mutations, the BRCA mutational status of 149 non-mucinous and non-borderline OC and their clinical-pathological features were evaluated. BRCA1 and BRCA2 mutational profiles, either for sequence variants or copy number alterations, were evaluated by amplicon next-generation sequencing (NGS) technology. Results: 29 (19.5%) patients carried a gBRCA mutation (12.7% BRCA1 and 6.7% BRCA2). 26 (17.5%) patients presented a sBRCA mutation (6.7% BRCA1, 10% BRCA2, 0.6% BRCA1+BRCA2). Patients carrying a gBRCA mutation were slightly younger (57 years) than the others (60 years). The FIGO stage at the diagnosis was III-IV in 77.2% of cases, with no significant difference among subgroups. The most frequent histotype was serous for all the subgroups (93.1% in gBRCA, 84.6% in sBRCA, 77.7% in BRCA-negative, p = 0.08). 80.7% of sBRCA mutation carriers, 62.1% of gBRCA mutation carriers and 62.7% of BRCA-negative patients underwent upfront surgery (p = 0.46). 29.1% of sBRCA mutation carriers, 17.8% of gBRCA mutation carriers and 25.6% of BRCA-negative patients presented macroscopic residual disease after surgery (p = 0.68). Although non-statistically significant, gBRCA-associated OC were more likely to be platinum-sensitive (96.6%) than the other patients (92% in sBRCA and 87.1% in BRCA-negative patients). Overall, the median platinum-free interval (PFI) resulted shorter in sBRCA mutation patients compared to gBRCA and BRCA-negative patients (p = 0.051). No patient took PARP inhibitors as maintenance after the first line therapy. Also progression free survival 2 (PFS2) resulted shorter for sBRCA mutation patients (p = 0.008). Three sBRCA and 5 gBRCA mutation carriers took a PARP inhibitor as maintenance after the second line therapy. Finally, sBRCA mutated patients showed worse overall survival (OS) compared to the other subgroups (p = 0.014). Conclusions: Overall, 19.5% of OC patients presented a gBRCA mutation, while 17.5% of patients showed sBRCA mutations. sBRCA-related OC did not show significantly differences in clinical-pathological features (stage at diagnosis, histotype, time to surgery and residual after surgery). To our knowledge this is the first study showing shorter PFI, PFS2 and OS in patients carrying sBRCA mutations.
Abstract Study question Does assisted reproductive technology (ART) to achieve pregnancy after breast cancer (BC) adversely affect maternal or fetal outcomes in germline BRCA1/2 pathogenic variants (PVs) carriers? Summary answer This global study showed that ART is safe in BC survivors harboring BRCA1/2 PVs, with no apparent worsening of maternal prognosis or fetal outcomes. What is known already Very little information is currently available on the safety of fertility treatments in BC survivors harboring BRCA1/2 PVs. The previous published work on this topic included only 22 cases of patients who used any kind of ART to become pregnant; the small number of included patients did not allow for statistical analysis. Hence, concerns remain among physicians counseling young BRCA carriers with prior history of BC on the safety of using ART to attempt pregnancy Study design, size, duration International, multicenter, hospital-based, retrospective cohort study across 78 centers worldwide. The study included 4732 women harboring known BRCA1/2 PVs and diagnosed at ≤ 40 years with stage I-III BC between January 2000 and 2020 (Lambertini M et al., JAMA 2024;331:49-59). This specific analysis included 543 women with a pregnancy after prior history of BC harboring a BRCA1/2 PV. Participants/materials, setting, methods Among 543 young BRCA carriers with a pregnancy after BC, 436 conceived naturally and 107 using ART. ART procedures included embryo transfer under hormonal replacement therapy following oocyte or embryo cryopreservation at diagnosis, treatment with oocyte donation, ovulation induction and In-Vitro-Fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) carried out after anticancer treatments. Survival analyses compared patients achieving a pregnancy spontaneously (spontaneous pregnancy group) vs. using ART (ART group). Main results and the role of chance Of 107 pregnancies achieved through ART, 45 (42.1%) were obtained with oocytes or embryo cryopreserved at diagnosis, 33 (30.8%) with ovarian stimulation and IVF/ICSI after completion of anticancer therapies, 21 (19.6%) with embryo transfer following oocyte donation and for 8 ART type was missing. As compared to survivors in the spontaneous pregnancy group, those in the ART group were older at the time of conception (37.1 vs. 34.3 years, p < 0.001), had more often hormone receptor-positive BC (46 (43.4%) vs. 132 (30.8%), p = 0.016), and a longer median time from BC diagnosis to conception (4.2 vs. 3.3 years, p = 0.004). No statistically significant differences in pregnancy complications were observed between cohorts (p = 0.382). However, patients who conceived with ART had more miscarriages (12, 11.3%) than those who conceived spontaneously (38, 8.8%). The opposite was true for induced abortion (1 (0.9%) vs. 36 (8.3%), respectively). At a median follow up of 9.1 years (interquartile range 6.4-13.4), no detrimental effect of ART on disease-free survival (DFS) was observed with 13 DFS events observed among the 99 patients undergoing ART and 118 DFS events in patients with spontaneous pregnancy (log-rank p = 0.147). Limitations, reasons for caution Despite the global representation, this retrospective study included a small number of patients for this specific analysis. Nevertheless, this is the largest analysis to date investigating safety of ART in BC survivors harboring BRCA1/2 PVs. Wider implications of the findings Young BRCA carriers can be reassured that the use of ART to achieve pregnancy is safe. Oocyte/embryo cryopreservation in young BRCA carriers allows access to pre-implantation genetic testing, if the patients are interested. Trial registration number NCT03673306
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