Impact of Pregnancy on Breast Cancer Features and Prognosis.

BACKGROUND: pregnancy-associated breast cancer (PABC) affects one in 3000 pregnancies, often presenting with aggressive features. METHODS: We retrospectively evaluated a cohort of 282 young BC patients (≤45 years old) treated between 1995 and 2019, dividing them into three groups: nulliparous women, women with PABC (diagnosed within 2 years since last pregnancy) and women with BC diagnosed > 2 years since last pregnancy. This last group was further stratified according to the time between pregnancy and BC. The analysis encompassed histological factors (tumor size, histotype, grading, nodal involvement, multifocality, lympho-vascular invasion, hormone receptor expression, Ki-67 index, and HER2 expression), type of surgery and recurrence. RESULTS: Age at diagnosis was younger in nulliparous than in parous women (p < 0.001). No significant differences were noticed regarding histological characteristics and recurrences. At univariate analysis, nodal involvement (OR = 2.4; p < 0.0001), high tumor grade (OR = 2.6; p = 0.01), and lympho-vascular invasion (OR = 2.3; p < 0.05), but not pregnancy (OR = 0.8; p = 0.30), influenced DFS negatively. Multivariate analysis confirmed nodal involvement as the only negative independent prognostic factor for a worse DFS (OR = 2.4; p = 0.0001). CONCLUSIONS: in our experience, pregnancy is not an independent adverse prognostic factor for BC DFS.

Gynecological Cancers in Lynch Syndrome: A Comparison of the Histological Features with Sporadic Cases of the General Population.

Introduction: About 5% of endometrial cancers (ECs) are attributed to an inherited predisposition, for which Lynch syndrome (LS) accounts for the majority of cases. Women with LS have a 40−60% predicted lifetime risk of developing EC, in addition to a 40−80% lifetime risk of developing colorectal cancer and other cancers. In this population, the lifetime risk of developing ovarian cancer (OC) is 10−12%. Object: to compare the histopathological features of LS-associated EC and OC with sporadic cancers in order to evaluate whether there are differences in terms of age at diagnosis, site of occurrence in the uterus, histological type, stage at diagnosis, and tumor grading. Materials and methods: we compared data obtained from 96 patients with LS-associated gynecological cancers (82 with EC and 14 with OC) to a control group (CG) of 209 patients who developed sporadic EC, and a CG of 187 patients with sporadic OC. Results: The mean age at diagnosis of LS-associated EC and OC was much lower than in the control groups. In both groups with EC, the endometrioid histotype was the most frequently occurring histotype. However, among LS women there was a significantly higher incidence of clear cell tumors (11% versus 2.4% in the CG, p = 0.0001). Similar to the sporadic cancer cases, most of the LS-associated ECs presented at an early stage (89% of cases at FIGO I-II stage). In the LS group, the tumor frequently involved only the inner half of the endometrium (77% of cases, p < 0.01). In the LS group, 7.3% of ECs were localized to the lower uterine segment (LUS), whereas no cancer developed in the LUS in the CG. No serous OCs were diagnosed in the LS group (versus 45.5% in the CG, p = 0.0009). Most of the LS-associated OCs presented at an early stage (85% of cases at FIGO I-II stages, p < 0.01). Conclusion: LS-associated EC and OC seem to have peculiar features, occurring at a younger age and at an earlier stage. In LS, EC less frequently involves the outer half of the endometrium, with a more frequent occurrence in the LUS. The presence of clear cell EC was more frequently observed, whereas in OC, the predominant histotype was endometrioid.

Breast cancer treatment in mutation carriers: surgical treatment.

The surgical option which should be reserved for patients with BRCA1/2 mutation and breast cancer diagnosis is still debated. Several aspects should be considered before the surgical decision-making: the risk of ipsilateral breast recurrence (IBR), the risk of contralateral breast cancer (CBC), the potential survival benefit of prophylactic mastectomy, and the possible risk factors that could either increase or decrease the risk for IBR or CBC. Breast conservative treatment (BCT) does not increase the risk for IBR in BRCA mutation carriers compared to non-carriers in short term follow-up; however, an increased risk for IBR in carriers was observed in studies with long follow-up. In spite of the increased risk for IBR in patients who underwent BCT than patients with mastectomy, no significant difference in breast-cancer specific or overall survival was observed by local treatment type at 15 years. Patients with BRCA mutation had a higher risk for CBC compared with non-carriers and BRCA1-mutation carriers had an increased risk for CBC compared to BRCA2-mutation carriers. Bilateral mastectomy is intended to prevent CBC in BRCA mutation carriers, however, no difference in survival was found if a contralateral prophylactic mastectomy was performed or not. For higher-risk groups of BRCA mutated patients, a more-aggressive surgical approach may be preferable, but there are some aspects that should be considered in the surgical decision-making process. The use of adjuvant chemotherapy and performing oophorectomy are associated with a decreased risk for IBR. When considering the risk for CBC, three risk factors were associated with significantly decreased risk: the use of adjuvant tamoxifen, performing oophorectomy and older age at first breast cancer diagnosis. As a result, we could identify a group of patients that might benefit from a more aggressive surgical approach (unilateral mastectomy or unilateral therapeutic mastectomy with concomitant contralateral prophylactic mastectomy). For women with BRCA mutations candidate to mastectomy, preservation of the nipple-areola complex (NAC) may be highly important due to the generally younger age at time of surgery. Concerning the oncological safety, nipple sparing mastectomy (NSM) is an acceptable option, with no evidence of compromise to oncological safety at short-term follow-up. The evaluation of surgical treatment in breast cancer patients with BRCA 1/2 mutation, should include several issues, namely the current evidence of adequate oncological safety of BCT in BRCA mutated patients; the increased risk for CBC especially in BRCA1 carriers; the feasibility on NSM with a greater patient's satisfaction for cosmetic results with no evidence of compromised oncological safety and, finally, the awareness that breast radiotherapy might increase the risk of complications in a possible subsequent mastectomy with immediate breast reconstruction.

Treatment options for pregnant women with ovarian tumors.

Diagnosis of ovarian mass during pregnancy is a rare event. Treatment of ovarian malignancies during pregnancy depends on histology, grade, stage, and gestational weeks. When possible, surgical excision is indicated, and sometimes, fertility-sparing surgery is recommended. Administration of systemic treatment before or after surgery is indicated as in nonpregnant women. Preliminary data suggest that platinum salts and taxanes are safe during pregnancy. Management of ovarian tumors in pregnancy requires a multidisciplinary approach to guarantee an optimal treatment for the mother and the fetus.

Strategies for fertility preservation in young early breast cancer patients.

Diagnosis of breast cancer in young women poses a threat to fertility. Due to a recent trend of delaying pregnancy, an increasing number of breast cancer patients in reproductive age wish to bear children. Health care providers have the responsibility to know how to manage fertility issues in cancer survivors. Oncofertility counseling is of great importance to many young women diagnosed with cancer and should be managed in a multi-disciplinary background. Most of young breast cancer patients are candidate to receive chemotherapy, which could lead to premature ovarian failure. A baseline evaluation of ovarian reserve may help in considering the different fertility preservation options. The choice of the suitable strategy depends also on age, type of chemotherapy, partner status and patients' motivation. Various options are available, some established such as embryo and oocyte cryopreservation, some still experimental such as ovarian tissue cryopreservation and ovarian suppression with GnRHa during chemotherapy. An early referral to a reproductive specialist should be offered to patients at risk of infertility who are interested in fertility preservation.