A prospective, multicenter, randomized, double-blind placebo-controlled trial on purified and specific Cytoplasmic pollen extract for hot flashes in breast cancer survivors.

OBJECTIVE: evaluate the efficacy and tolerability of PureCyTonin against hot flashes (HF) in breast cancer survivors (BCS). METHODS: a prospective, multicenter, randomized, double-blind placebo-controlled trial was conducted in Italy. INTERVENTIONS: administration of PureCyTonin or placebo, for 3 months. Effectiveness was investigated through the compilation of a daily diary for HF and of validated questionnaires (Menopause Rating Scale (MRS), Pittsburgh Sleep Quality Index (PSQI), Visual Analogical Scales (VAS) for HF, sweating, irritability, fatigue, sleep, quality of life), carried out before starting the treatment (T0), after 1 month (T1) and after 3 months (T2). Any side effects and HF diary were recorded at each visit. RESULTS: 19 women were randomized to receive PureCyTonin and 20 to placebo. At T2 compared to T0, in the PureCyTonin group, we found a reduction in the number of HF (p = 0.02) measured by daily diary. An improvement in the subjective perception of women regarding HF intensity (p = 0.04), sweat nuisance (p = 0.02), irritability (p = 0.03) and fatigue (p = 0.04) was observed through VAS scale measurement at T2 compared to T0.The total MRS score was significantly better in the PureCyTonin group at T1 (p = 0.03) compared to T0. CONCLUSIONS: PureCyTonin significantly reduces HF number after 3 months of therapy in BCS and it is well-tolerated.

Emerging evidence on the role of breast microbiota on the development of breast cancer in high-risk patients.

Cancer is a multi-factorial disease, and the etiology of breast cancer (BC) is due to a combination of both genetic and environmental factors. Breast tissue shows a unique microbiota, Proteobacteria and Firmicutes are the most abundant bacteria in breast tissue, and several studies have shown that the microbiota of healthy breast differs from that of BC. Breast microbiota appears to be correlated with different characteristics of the tumor, and prognostic clinicopathologic features. It also appears that there are subtle differences between the microbial profiles of the healthy control and high-risk patients. Genetic predisposition is an extremely important risk factor for BC. BRCA1/2 germline mutations and Li-Fraumeni syndrome are DNA repair deficiency syndromes inherited as autosomal dominant characters that substantially increase the risk of BC. These syndromes exhibit incomplete penetrance of BC expression in carrier subjects. The action of breast microbiota on carcinogenesis might explain why women with a mutation develop cancer and others do not. Among the potential biological pathways through which the breast microbiota may affect tumorigenesis, the most relevant appear to be DNA damage caused by colibactin and other bacterial-derived genotoxins, ß-glucuronidase-mediated estrogen deconjugation and reactivation, and HPV-mediated cancer susceptibility. In conclusion, in patients with a genetic predisposition, an unfavorable breast microbiota may be co-responsible for the onset of BC. Prospectively, the ability to modulate the microbiota may have an impact on disease onset and progression in patients at high risk for BC.

Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer.

BRCA1/2 mutations account for 5 to 10% of breast and 15% of ovarian cancers. Various guidelines on BRCA1/2 genetic counseling and testing have been issued, and the criteria have evolved over the years. Oncogenetic counseling aims to inform patients about the possibility and implications of undergoing predictive testing and risk management programs. We analyzed a cohort of 50 subjects with a previous personal history of breast or ovarian cancer who had not been tested for BRCA1/2 mutations at the time of diagnosis but were found eligible according to the most recent guidelines. All patients were offered pre-test oncogenetic counseling and BRCA1/2 genetic testing. The mean time from cancer diagnosis to genetic counseling was over 10 years. We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. The offer of BRCA testing was well accepted by our study population, despite the many years since the cancer diagnosis. With the perspective of further broadening the access criteria to genetic testing, it is important to understand how to best approach pre-test counseling in long-surviving patients with a previous diagnosis of cancer.

Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality of women with hormone-receptor-positive tumors, but poor adherence remains a significant problem. The aim of this study was to analyze AET side effects and their impact on adherence to treatment. METHODS: A total of 373 breast cancer patients treated with AET filled out a specific questionnaire during their follow up visits at the Breast Unit of our Centre. RESULTS: Side effects were reported by 81% of patients, 84% of those taking tamoxifen and 80% of those taking aromatase inhibitors (AIs). The most common side effect in the tamoxifen group was hot flashes (55.6%), while in the AI group it was arthralgia (60.6%). The addition of GnRH agonists to both tamoxifen and AI significantly worsened all menopausal symptoms. Overall, 12% of patients definitively discontinued AET due to side effects, 6.4% during the first 5 years and 24% during extended therapy. Patients who had previously received chemotherapy or radiotherapy reported a significantly lower discontinuation rate. CONCLUSIONS: AET side effects represent a significant problem in breast cancer survivors leading to irregular assumption and discontinuation of therapy. Adherence to AET may be improved by trustful patient-physician communication and a good-quality care network.

FOXA1 in Breast Cancer: A Luminal Marker with Promising Prognostic and Predictive Impact.

The present review focuses on the function of the forkhead protein FOXA1 in breast cancer (BC) in relation to steroid hormone receptors. We explored the currently available analytic approaches for FOXA1 assessment both at gene and protein levels, comparing the differences between the available techniques used for its diagnostic assessment. In addition, we elaborated on data regarding the prognostic and predictive role of this marker in BC based on several studies that evaluated its expression in relation to the outcome and/or response to therapy. FOXA1, similar to the androgen receptor (AR), may have a dual role in BC according to hormonal status. In luminal cancers, its expression contributes to a better prognosis, while in triple-negative breast cancers (TNBC), it implies an adverse outcome. Consequently, we observed that FOXA1-positive expression in a neoadjuvant setting may predict a lack of response in luminal BC as opposed to TNBC, in which FOXA1 allegedly increases its chemosensitivity. In conclusion, considering its accessible and convenient identification by immunohistochemistry, its important impact on prognosis, and its suitability to identify patients with different responses to chemotherapy, we propose that FOXA1 could be tested in routine diagnostics as an additional prognostic and predictive marker in BC.

Surgery after Neoadjuvant Chemotherapy: A Clip-Based Technique to Improve Surgical Outcomes, a Single-Center Experience.

BACKGROUND: This study aims to describe the surgical management of breast cancer patients after neoadjuvant chemotherapy, with attention to the impact on surgical outcomes of a clip-based marking technique. METHODS: Patients who underwent NACT at the Breast Unit of the A. O Ordine Mauriziano of Turin from January 2018 and had a surgical intervention by January 2022 were included. Data on the feasibility of clip insertion, after-treatment visibility, and successful removal during surgery were collected prospectively. Surgical outcomes in terms of breast-conserving surgery and axillary dissection reduction were described. RESULTS: In 51 patients who had surgery after NACT, 55 clips were placed (34 breast and 21 axillary clips). Ultrasound visibility of the clips was optimal (91%) as well as preoperative localization and retrieval within the surgical specimen. Moreover, the use of the clip positively affected surgical outcomes. In our study, clip insertion allowed to avoid mastectomy and axillary dissection in patients with a complete radiological response. CONCLUSIONS: In our findings, the use of breast and/or lymph node clips has proved to be a simple and effective method to improve surgical conservative management of breast cancer patients after NACT.

The Role of Trastuzumab in Patients with HER2 Positive Small (pT1mi/a) Breast Cancers, a Multicenter Retrospective Study.

The treatment with adjuvant Trastuzumab in patients diagnosed with HER2+ small breast cancers is controversial: limited prospective data from randomized trials is available. This study aims to measure the effect of Trastuzumab in the early stages of breast cancer (pT1mic/a pN0/1mi) in terms of disease recurrence and to identify which are the factors that most affect the prognosis of small HER2+ tumors. One hundred HER2+ pT1mic-pT1a breast cancer patients who were treated in three Turin Breast Units between January 1998 and December 2018 were retrospectively selected and reviewed. Trastuzumab was administered to 23 patients. Clinicopathological features and disease-free survival (DFS) were compared between different subgroups. The primary outcome was the disease recurrence rate. Median follow-up time was 86 months. Compared to pT1a tumors, pT1mic lesions had a higher tumor grade (84% of pT1mic vs. 55% of pT1a; p = 0.003), a higher Ki-67 index (81% vs. 46%; p = 0.007) and were more frequently hormone receptor (HR) negative (69% vs. 36%, p = 0.001). Disease recurrence rate was significantly lower among patients who received adjuvant Trastuzumab (p = 0.02), with this therapy conferring an 85% reduction in the risk of relapse (HR 0.15; p = 0.02). Among the patients who did not receive adjuvant Trastuzumab, the only factor significantly associated with an increased risk of developing a recurrence was the immunohistochemical (IHC) subtype: in fact, HR- HER2+ tumors showed a risk seven times higher of relapsing (HR 7.29; p = 0.003). Adjuvant Trastuzumab appears to reduce the risk of disease recurrence even in small HER2+ tumors. The adjuvant targeted therapy should be considered in patients with HR- HER2+ tumors since they have the highest risk of recurrence, independently from size and grade.

Evaluation of the ability of the Clinical Treatment Score at 5 years (CTS5) compared to other risk stratification methods to predict the response to an extended endocrine therapy in breast cancer patients.

PURPOSE: Extension of adjuvant endocrine therapy (ET) reduces the risk of recurrence in women diagnosed with ER-positive breast cancers, but a significant benefit is unlikely to happen to all individual patients. This study is aimed at evaluating the ability of different clinical late distant recurrence (LDR) risk stratification methods and in particular the clinical treatment score at 5 years (CTS5) to predict the response to extended adjuvant ET. METHODS: 783 patients diagnosed with ER+ BC between 1988 and 2014 at Umberto I Hospital of Turin, of which 180 received an extended adjuvant ET, were retrospectively selected. They were stratified according to pT, pN, disease stage, tumor grade, Ki67 level, progesterone receptor status and CTS5. The primary endpoint was LDR rate. LDR rates according to ET duration were confronted in each subgroup. RESULT: The median duration of extended ET was 7 years (6-10). Median follow-up from diagnosis was 9 years (6-26). Retrospective risk stratification according to tumor size, nodal status, disease stage, tumor grade, Ki67 level, and progesterone receptor status did not appear to be able to predict the response to extended ET. In the CTS5 high-risk subgroup instead, the risk of developing an LDR was significantly lower in the patients who underwent extended ET compared to standard ET (HR 0.37, 95% CI 0.15-0.91), while no significant benefit was demonstrated for low and intermediate-risk patients. CONCLUSIONS: Risk stratification according to CTS5 appeared to be predictive of the response to extended endocrine therapy in our population of real-life pre and postmenopausal patients.

Validation of CTS5 on a Retrospective Cohort of Real-Life Pre- and Postmenopausal Patients Diagnosed With Estrogen Receptor-Positive Breast Cancers: Is It Prognostic?

BACKGROUND: More than 50% of estrogen receptor (ER)-positive breast cancer (BC) distant recurrences (DR) develop after the completion of 5 years of adjuvant endocrine therapy (ET). Its extension is beneficial on disease-free survival and overall survival but increases therapy-related side effects. Selecting patients who could benefit the most from an extended regimen has become an increasing need. Clinical Treatment Score at 5 Years (CTS5) is a prognostic tool using clinicopathologic data to estimate DR risk after 5 years of ET for ER+ BC. We sought to validate the prognostic value of CTS5 in a retrospective cohort of real-life pre- and postmenopausal patients diagnosed with ER+ BC. PATIENTS AND METHODS: CTS5 was calculated for 603 patients diagnosed with ER+ BC at Umberto I Hospital of Turin and DR-free after 5 years of ET. Primary endpoint was late DR (LDR) rate. RESULTS: Median follow-up was 8 years (range, 6-26 years). The 426 postmenopausal women were categorized by CTS5 as follows: 152 low risk, 139 intermediate risk, and 135 high risk. LDR rates were 3.9%, 7.2%, and 15.6%, respectively. CTS5 results were prognostic for LDR: patients with CTS5-high showed a fourfold risk of developing an LDR compared to patients with CTS5-low (hazard ratio, 4.48; 95% confidence interval, 1.80-11.1). The same analysis was conducted for the 177 premenopausal women: 88 low risk, 40 intermediate risk, and 49 high risk. LDR rate were 5.6%, 7.5%, and 20.4%, respectively, proving CTS5 to be prognostic for premenopausal patients as well (CTS5-high vs. CTS5-low: hazard ratio, 3.40; 95% confidence interval, 1.06-11.0). CONCLUSION: CTS5 was shown to be prognostic of the risk of LDR in our population of real-life pre- and postmenopausal patients. Our results support its use in clinical practice to better tailor the prescription of extended ET.

Extended endocrine therapy in premenopausal breast cancer patients: Where are we now?

Approximately 25% of new breast cancers are diagnosed in premenopausal patients, 50%-70% presenting as estrogen receptor-positive (ER+) breast tumors. Five-year adjuvant endocrine therapy (ET) with Tamoxifen is the cornerstone treatment for those patients but the evidence that up to 50% of ER + breast cancer distant recurrences develop after this time has now raised some questions. ATLAS and aTTom trials are the only two studies addressing the extension of Tamoxifen beyond 5 years in premenopausal patients. They showed significant DFS and OS benefits at a cost of increased rates of endometrial cancer and pulmonary embolus. Therefore, the selection of the patients at higher recurrence risk and hence deemed to get the most benefit from an extended endocrine therapy has become a major concern. Many clinical and genomic prognostic tools have shown validity in identifying patients at high late recurrence risk, but only the BCI prognostic score was shown to also be predictive of response to extended endocrine therapy. Nevertheless, all the evidence available on extended endocrine therapy in premenopausal patients was derived from trials in which patients were treated with tamoxifen alone and are hardly applicable to the current clinical scenario. In fact, the results of the SOFT and TEXT trials demonstrated the superiority of the addition of ovarian function suppression (OFS) and its association with the aromatase inhibitor (AI) Exemestane to Tamoxifen alone. However, the introduction in the clinical practice of AI + OFS-based endocrine therapy for the premenopausal patients will very soon lead to an impasse since neither data exist on extended therapy after this treatment schedule nor is there an ongoing trial intended to obtain new evidence.

Pseudoangiomatous Stromal Hyperplasia (PASH) of the Breast: An Uncommon Finding in an Uncommon Patient.

BACKGROUND Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign breast lesion. CASE REPORT PASH is reported in a young female in treatment for neurological diseases with multi-drug therapy (clonazepam, valproate and risperidone). Her menstrual cycles are irregular, and she reached menarche very late. CONCLUSIONS The higher PASH prevalence in premenopausal woman (the majority of whom are actively taking oral contraceptive pills), in 24% to 47% of men with gynecomastia and during pregnancy supports a hormonal etiology; the interaction between clonazepam, valproate, risperidone and progesterone could increase the level of progesterone that could stimulate PASH growth.

Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?

Recent studies demonstrated the possibility to avoid axillary dissection (ALND) in selected patients with one or two metastatic nodes. Otherwise, patients with positive nodal ultrasound-guided fine-needle aspiration cytology (US-FNAC) currently undergo ALDN. The aim of this study is to quantify the nodal burden in patients with positive US-FNAC treated with ALND and to evaluate if clinical or pathological characteristics associated with low nodal involvement can be identified. This is a multicentric retrospective study involving 297 patients who underwent ALND because of a positive preoperative US-FNAC. A total of 157 patients showed bulky axillary lymph nodes at diagnosis, and 70% of them had three or more metastatic nodes. One hundred and forty patients had a clinically negative axilla and in 50% of them, 4 or more metastatic nodes were found with axillary dissection. Overall, the median number of metastatic nodes was 5. Favorable pathological characteristics of tumors were found in patients with only one or two metastatic nodes: smaller primary tumor, a lower proportion of grade 3, invasive lobular carcinomas and a higher proportion of low-Ki67 tumors. In the group of patients with clinically negative axilla and potentially meeting ACOSOG Z0011 criteria, 22 (31%) showed less than three metastatic axillary nodes. A preoperative positive axillary FNAC is associated with a metastatic nodal burden significantly higher than in patients with positive sentinel lymph node biopsy (SLNB). Nevertheless, about 30% of patients with cN0 axilla, positive axillary FNAC performed because of suspicious nodes on imaging, T1-2 primary tumor and breast-conserving surgery showed less than three metastatic axillary nodes, thus meeting ACOSOG Z0011 trial's criteria and therefore would be eligible for skipping ALND according to current guidelines.

Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy.

Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptoms and has been shown to prevent bone loss and fracture. The progestogen is added to provide endometrial protection in women with an intact uterus. After the publication of the initial WHI (Women's Health Initiative) results in 2002 reporting an overall increased risk of breast cancer, many women discontinued HRT. Despite the re-analysis of the results by subgroups of patients and updates with extended follow-up, much controversy remains, which we will analyze later in the text. Different types of estrogen or progestogen, as well as different formulations, doses, and durations, may play a role in HRT's effects on breast tissue. Evidence states that conjugated equine estrogen (CEE), compared to estro-progestin therapy, shows a better profile risk (HR 0.79, CI 0.65-0.97) and that, among different type of progestins, those structurally related to testosterone show a higher risk (RR 3.35, CI 1.07-10.4). Chronic unopposed endometrial exposure to estrogen increases the risk of endometrial hyperplasia and cancer, whereas the association with progestins, especially in continuous combined regimen, seems to reduce the risk (RR 0.71, CI 0.56-0.90). HRT was also associated with a protective effect on colon cancer risk (HR 0.61, CI 0.42-0.87). Data about ovarian and cervical cancer are still controversial.

Nipple-sparing mastectomy: external validation of a three-dimensional automated method to predict nipple occult tumour involvement on preoperative breast MRI.

BACKGROUND: Preoperative evaluation of nipple-areola complex (NAC) tumour involvement is crucial to select patients candidates for nipple-sparing mastectomy. Our aim was to validate a previously developed automated method able to compute the three-dimensional (3D) tumour-to-NAC distance (the most predictive parameter of nipple involvement), using magnetic resonance imaging (MRI) datasets acquired with a scanner and protocol different from those of the development phase. METHODS: We performed a retrospective analysis of 77 patients submitted to total mastectomy and preoperatively studied with MRI. The new method consisted of automated segmentation of both NAC and tumour and subsequent computation of the 3D distance between them; standard manual two-dimensional segmentation was independently performed. Paraffin-embedded section examination of the removed NAC was performed to identify the neoplastic involvement. The ability of both methods to discriminate between patients with and without NAC involvement was compared using receiver operating characteristic (ROC) analysis. RESULTS: The 3D tumour-to-NAC distance was correctly computed for 72/77 patients (93.5%); tumour and NAC segmentation method failed in two and three cases, respectively. The diagnostic performance of the 3D automated method at best cut-off values was consistently better than that of the 2D manual method (sensitivity 78.3%, specificity 71.4%, positive predictive value 87.5%, negative predictive value 56.3%, and AUC 0.77 versus 73.9%, 61.2%, 47.2%, 83.3%, and 0.72, respectively), even if the difference did not reach statistical significance (p = 0.431). CONCLUSIONS: The introduction of the 3D automated method in a clinical setting could improve the diagnostic performance in the preoperative assessment of NAC tumour involvement.

Concerns and Expectations of Risk-Reducing Surgery in Women with Hereditary Breast and Ovarian Cancer Syndrome.

Hereditary Breast and Ovarian Cancer syndrome (HBOC) carriers face complex decisions, which might affect their fertility and body image. Using an anonymous 40-items questionnaire we evaluated the expectations and concerns about Risk-Reducing Surgery (RRS) in 204 carriers. Participants are well-informed about the options to manage cancer risk, and women with previous cancer are more concerned with screening failure. Satisfaction with RR Mastectomy is high, even if many carriers are unsatisfied with reconstructed breast feel and nipple-areola complex tactile sensation and those with previous breast cancer report a change in their sexual habits. The decrease of libido and vaginal dryness are the most complained symptoms after RR Salpingo-Oophorectomy. Nevertheless, most carriers would choose RRS again, due to cancer risk or screening-related stress reduction. Women who deferred RRS are more afraid of menopausal symptoms and cancer risk than those who had undergone or declined surgery. Women who declined RRS feel well-informed and trust screening procedures. In conclusion, HBOC carriers consider themselves well-informed and able to choose the best option for their condition, would choose RRS again because of cancer risk and screening-related stress reduction, and those who delay RRS face a higher preoperative level of concern and need support.

Satisfaction and Impact on Quality of Life of Clinical and Instrumental Surveillance and Prophylactic Surgery in BRCA-mutation Carriers.

INTRODUCTION: BRCA 1 and 2 mutation carriers are invited to follow intensive clinical and instrumental surveillance programs or are offered prophylactic breast and ovarian surgery. These recommendations impact many aspects of their life. This study aims to evaluate the satisfaction with surveillance and prophylactic surgery and the impact of these procedures on the quality of life. PATIENTS AND METHODS: An anonymous questionnaire was administered to 174 BRCA1-2 mutation carriers. RESULTS: A total of 95% of women comply with the scheduled checks every 6 months. Periodic examinations are considered useful for early diagnosis of breast/ovarian cancer by 91.5% of responders. Among those women who received prophylactic breast surgery, 95% believe that this procedure can reduce cancer risk, but only 65% were completely satisfied by the cosmetic outcome. Among women who underwent prophylactic ovarian surgery, 90.5% would choose it again, mainly owing to a lower degree of concern about ovarian cancer risk. The early onset of menopausal symptoms was the most frequently reported side effects, but only 21% of patients use any treatment to relieve them. CONCLUSION: Women who follow a surveillance program show a good level of satisfaction, thanks to the lowering of concerns of cancer risk. The degree of satisfaction about the prophylactic surgery is generally high. Risk-reducing mastectomy is usually well-accepted, despite the fact that cosmetic results are not entirely satisfactory. Bilateral salpingo-oophorectomy may impact on quality of life because of the symptoms associated with early surgical menopause, even if it can be treated with hormonal replacement therapies.

Nipple-Sparing Mastectomy: Reliability of sub-areolar sampling and frozen section in predicting occult nipple involvement in breast cancer patients.

INTRODUCTION: The oncological safety of nipple-areolar complex (NAC) preservation is a concern in the mastectomies performed for cancer indication. The detection of tumor cells during the intraoperative frozen section examination (IE) of sub-areolar/nipple tissue (SAT) leads to the removal of NAC, but frequently the final histology of the nipple is negative for malignancy. This study aims to evaluate the accuracy of SAT examination in predicting occult NAC involvement in case of Nipple-Sparing Mastectomy (NSM). METHODS: The study includes 76 NSM. We evaluated the concordance between histopathologic features of frozen and paraffin-embedded SAT sections. Moreover, we examined the "true margin" (TM), defined as the measurement of the distance between the tumor margin and the edge of the SAT. A margin >1 mm was considered negative. RESULTS: In 26/76 cases the IE of the SAT was positive. At the final histology, the NAC was negative in 57.7% of cases. The concordance between frozen and paraffin section examination of the SAT was 92.1%. The three false-positives were low-grade DCIS at the IE, and negative or DIN1a on permanent section. A negative TM seems to predict for a negative NAC (6/6). CONCLUSIONS: The detection of a low-grade DCIS at the IE of the SAT may not be confirmed at the permanent section examination; we recommend caution in removing the NAC in these cases. The evaluation of the TM may improve the accuracy of SAT analysis in predicting occult NAC involvement; in our series, a TM wider than 1 mm correlates with a negative NAC.

Unexpected uterine leiomyosarcoma in a woman with multiple myomas treated with ulipristal acetate: case report and literature review.

Ulipristal acetate (UPA) has been recognized as an alternative strategy to surgery in the management of symptomatic women with uterine fibroids. We present a case report on a woman with hereditary fibrinogen deficiency exclusively treated with UPA for myoma-related menorrhagia and abdominal pain, who subsequently underwent a hysterectomy because of clinical worsening. A FIGO IB uterine leiomyosarcoma was found among multiple myomas. A review of the literature found two other cases of uterine leiomyosarcoma in patients treated with UPA: clinical data are reported. The aim of this case report is to increase clinicians' awareness that, although rare, leiomyosarcoma can develop in a uterus with multiple myomas and no reliable diagnostic tools exist yet. Thus, a clinical and instrumental careful reevaluation and patient counseling should be a priority when planning to repeat UPA treatment cycles.

Vaginal Atrophy in Breast Cancer Survivors: Attitude and Approaches Among Oncologists.

BACKGROUND: Vulvovaginal atrophy (VVA) is a relevant problem for breast cancer survivors (BCSs), in particular for those who receive aromatase inhibitors (AIs). We conducted a survey, to assess the attitude of oncologists toward the diagnosis and treatment of VVA in BCSs. MATERIALS AND METHODS: In 2015, 120 computer-assisted Web interviews were performed among breast oncologists. RESULTS: According to oncologists' perceptions, 60% of postmenopausal BCSs and 39.4% of premenopausal BCSs will suffer from VVA. Despite that none of the physicians considered VVA as a transient event or a secondary problem in BCSs, only half of the oncologists (48%) directly illustrated VVA to the patients as a possible consequence. Forty-one percent of the oncologists refer BCSs to gynaecologist to define VVA treatment, whereas 35.1% manages it alone. Nonhormonal treatments are preferred by most oncologists (71%). The main reason not to prescribe vaginal estrogen therapy in BCSs is the fear of increased cancer recurrence, the possible interference with tamoxifen, or AIs and the fear of medical litigation. CONCLUSION: VVA is a relevant problem for BCSs. Great effort should be done to correctly inform health care providers about VVA problems and on the different possible available treatments.

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.