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Background. Adjuvant endocrine therapy (AET) significantly reduces breast cancer recurrence and mortality in women with hormone receptor positive tumors, but poor adherence to treatment remains a significant problem. The aim of this study is to analyze AET side effects, their impact on adherence to treatment and possible support strategies. Methods. The study included 373 breast cancer patients treated with AET, who were asked to fill out a specific questionnaire during their follow up visits at the Breast Unit of "Mauriziano Umberto I” Hospital. Results. Side effects were reported by 82% of patients, 81% of those taking tamoxifen and 67.5% of those taking aromatase inhibitors (AI). The most common side effect in tamoxifen group were hot flashes (52%), while it was arthralgia in AI group (60%). The addition of GnRH agonist to both tamoxifen and AI significantly worsened menopausal symptoms and premenopausal women were significantly more likely to report side effects than those who were menopausal at diagnosis. Globally, 21% of patients considered to discontinue therapy due to side effects, 8.2% reported an irregular assumption and 12% definitively discontinued the treatment. The discontinuation rate was 6.4% during the first 5 years of treatment and 24% during extended therapy. Arthralgia was the main side effect which led patients to discontinue AET. Most patients felt well supported during follow up visits, but only 9% used the dedicated menopause service and 15% received psychological support. Conclusions. AET side effects significantly affect the quality of life of breast cancer survivors leading to irregular assumption and discontinuation of therapy, but our study showed that adherence to AET may be improved by proper patient-physician communication and a good quality care network. The challenge is to be more aware of treatment-related side effects and to offer therapies to improve their tolerance and adequate medical and psychological support.

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.

Simple Summary Treatment of small HER2+ breast cancers with adjuvant Trastuzumab is still controversial. This study aims to measure the effect of Trastuzumab in early stages of breast cancer (pT1mic/a pN0/1mi) in terms of disease recurrence and to identify which factors most affect the prognosis of small HER2+ tumors. We retrospectively selected and reviewed 100 HER2+ pT1mic-pT1a breast cancer patients with a median follow-up of 86 months. In our study the primary outcome was the disease recurrence rate, which appeared to be significantly lower among patients who received adjuvant Trastuzumab. Among the patients who did not receive adjuvant Trastuzumab, HR− HER2+ tumors showed a risk seven times higher of relapse. The results of our study indicate that adjuvant Trastuzumab reduces the risk of developing a disease recurrence even in small HER2+ tumors. Adjuvant targeted therapy should be considered in patients with HR− HER2+ tumors, the category with the highest risk of recurrence. Abstract 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.

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.

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.

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.

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.

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.

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.

Patient: Female, 30-year-old Final Diagnosis: Pseudoangiomatous stromal hyperplasia (PASH) Symptoms: Breast mass Medication: — Clinical Procedure: Lumpectomy Specialty: Obstetrics and Gynecology Objective: Unknown ethiology 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.

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.

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.

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.

Women with a life expectancy ≥10 years and no diagnosis/history of breast cancer who are considered to be at increased risk for breast cancer should receive counseling to decrease breast cancer risk, considering lifestyle factors, therapy with risk reduction agents, and risk reduction surgery (in BRCA1/2 mutation carriers).Bilateral risk-reducing mastectomy decreases the risk of developing breast cancer by at least 90%; it should be proposed to carefully selected women at high risk for breast cancer considering BRCA1/2 or other genetic mutations and previous history of LCIS. In current practice, atypical hyperplasia is not an indication for prophylactic mastectomy.Bilateral risk-reducing salpingo-oophorectomy decreases the risk of developing ovarian and fallopian cancer by 85–95% and breast cancer by 50% in BRCA1/2 mutation carriers when performed in premenopausal age. Peritoneal washing should be performed at surgery, and pathologic assessment should include fine sectioning of the ovaries and fallopian tubes. The additional benefit of concurrent hysterectomy is not clear at the time. In women with no personal history of breast cancer, short-term HRT use does not negate the protective effect of RRSO on subsequent breast cancer risk, and it should be offered until the time of expected natural menopause.

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.

Nipple-areola sparing mastectomy (NSM) is increasingly used in patients with non-locally advanced breast carcinoma. Literature data on the preoperative assessment of the nipple-areola complex (NAC) are inconsistent.Out of 1359 patients submitted to total mastectomy between 2001 and 2010, we selected 61 patients whose pre-operative mammogram (MX) was available (MX group) and 39 patients who underwent preoperative breast magnetic resonance imaging (magnetic resonance imaging (MRI) group). The rate of NAC involvement, the value of MX and MRI to predict NAC involvement and the performance of the Schecter's and Loewn's algorithms for the prediction of NAC involvement were evaluated.In the combined MX and MRI groups, NAC involvement was found in 14% of the cases. At univariate analysis, tumour stage (p value: 0.03), central tumour location (p value: 0.004), presence of NAC retraction (p value: 0.001) and tumour-NAC distance (p value: 0.006) were associated with NAC involvement, but only the latter parameter retained statistical significance at multivariate analysis (p value: 0.05). Tumour-NAC distance was a key predictor of NAC involvement, with a negative predictive value of 94% for MX and of 100% for MRI when the cut-off was set at 10mm. Overall, the performance of Schecter's and Loewn's algorithms was respectively lower and similar as compared to the original series.Occult tumour involvement of the NAC is detected in a minority of breast cancer patients submitted to mastectomy. A tumour-NAC distance ≥ 10 mm by MRI may help select patients candidate to NSM.

The objective of this study is to investigate if changes in cognitive functions can be recognised in patients undergoing chemotherapy for breast cancer. Forty women with breast cancer and without depression underwent cognitive evaluation before and after 6 months of chemotherapy; emotional evaluation was performed before and after 1, 3 and 6 months of chemotherapy. Self-reported cognitive deficit evaluation was included. Global cognitive functioning before starting chemotherapy was good. After 6 months of treatment there was a significant decline in some cognitive functions, particularly involving the attention subdomain. Objective cognitive deficit resulted independent from the emotional status. On the contrary, self-perceived mental dysfunction was unrelated to the objective cognitive decline, but it was associated with depression and anxiety. Breast cancer chemotherapy can induce domain-specific cognitive dysfunction. Patients' self-perception of mental decline is unrelated to objective cognitive deficit. Breast cancer patients negatively judge their cognitive performances if they have a negative emotional functioning.

Breast cancer (BC) is the most commonly diagnosed invasive cancer among women; in developed countries, BC occurs in one out of eight women during her lifetime. Many factors, both genetic and non-genetic, determine a woman's risk of breast cancer and several mathematical models have been proposed that determine the risk. It is important to identify those at high risk, as there are now effective preventive strategies, such as chemoprevention therapy and risk-reduction surgery. Risk-reduction agents are recommended for women aged 35 years or more who are at high risk of breast cancer. Tamoxifen is presently deemed to be the agent of choice. However, raloxifene may be preferable, at least for some postmenopausal women, because of its lack of effect on the endometrium and the reduced incidence of venous thromboembolic events compared with tamoxifen. Prophylactic surgery has been widely investigated. Bilateral mastectomy decreases the risk of developing breast cancer by approximately 90% in women at moderate or high risk and in known BRCA1/2 mutation carriers. This review summarizes the recent advances in the identification of women at high risk of developing breast cancer and reports on the strategies used to prevent breast cancer; the risk-benefit balance of such preventive choices is also briefly analyzed.

Breast cancer survivors (BCSs) often suffer from menopausal symptoms induced by systemic treatments, with a consequent negative effect on quality of life. Since the introduction of aromatase inhibitors as the standard therapy for hormone-dependent tumors, genitourinary syndrome of menopause (GSM) has become a main problem for BCSs. This new terminology refers to the wide range of vaginal and urinary symptoms related to menopause, which can be relieved by estrogen therapy. Unfortunately, systemic hormone therapy is contraindicated for BCSs and also vaginal estrogens at standard dosage might influence the risk of recurrence because they cause a significant increase of circulating estrogens. Nonhormonal vaginal moisturizers or lubricants are the first choice for BCSs but only have limited and short-term efficacy. New strategies of management of GSM are now available, including: (1) low-dose or ultra low-dose vaginal estrogens; (2) oral selective estrogen receptor modulators (ospemifene); (3) androgen therapy; (4) physical treatment with vaginal laser; and (5) psychosocial interventions. In this review we discuss and analyze these different options.

Androgen receptors (ARs) are frequently expressed in breast cancer (BC) cells, but their implication as a prognostic and/or predictive marker is still controversial. Preclinical studies suggest that the action of androgens is bidirectional: mainly proliferative, because circulating androgens are the precursors of estrogens, but also antiproliferative, because AR activation restrains ER activity inhibiting normal breast tissue growth. ARs play different roles at different stages of disease or in different subtypes of BC. ARs are expressed in up to 70 % of ER-positive BC and high levels of expression confer a survival advantage. Moreover, the increase of androgens that follows the blocking of androgen aromatization into estrogens by aromatase inhibitors (AIs) could contribute to their therapeutic efficacy in AR-positive cases. Up to 50 % of ER-negative BC are reported to be positive for ARs. Currently, epidemiological, clinical, and preclinical data on the role of androgens and ARs on this BC subtype are still controversial. In HER2-expressing cell lines, preclinical studies suggest that ARs have a proliferative effect, probably due to the cross talk between ARs and HER2 pathways. In conclusion, AR is an emerging target in breast cancer, with potential significance for therapeutic management of both primary and advanced disease.

Receiving cancer diagnosis can be devastating for many patients but thanks to advances in cancer therapies it is not a death sentence anymore. Cancer survival rates are increasing and life after cancer is a real chance for many patients worldwide. In Europe, about one third of cancer patients have a relative 5-year survival rate greater than 80 % [1]. Similar survival rates are seen in the United States, Canada and Australia. Lower survival rates in developing countries are most likely due to late diagnosis and limited availability of up-to-date standard treatments [2, 3].

Around 6 % of breast cancer cases occur in women younger than 40 years; these patients show specific issues compared to older women. The effects of local and systemic treatments such as the distortion of body image, sexuality complaints, and fertility reduction have a higher impact in this population of young women. Fertility issues should be discussed before starting any type of anticancer treatment. The optimal type of fertility preservation, the endocrine treatment duration, and the effect of subsequent pregnancies on breast cancer prognosis remain research priorities. Currently, fertility preservation techniques rely on cryopreservation of embryos, cryopreservation of mature oocytes, cryopreservation of ovarian tissue and on the administration of GnRHa concomitant to chemotherapy. Advantages and disadvantages of each technique must be evaluated in each single patient. Many studies have shown that pregnancy after breast cancer does not impair the prognosis, both in ER+ and ER− patients; a protective effect of pregnancy has even been suggested. Young patients should not be undertreated to satisfy their eagerness for pregnancy; physicians should share with them all the available options for fertility preservation and the evidence about safety of pregnancy after cancer, to make a customized and informed decision.

Fertility issues should be discussed with young women before the start of any anticancer treatment. The study is aimed to investigate the attitude on fertility among Italian oncologists and breast surgeons dealing with BCa, and to report the consensus achieved on specific statements.One hundred and sixty-two panelists anonymously expressed an opinion through a web-based platform on 19 statements based on the Delphi method.Ninety-one percent of oncologists considered important to discuss with patients about fertility issues and 83% believed estrogens could stimulate the growth of hidden cancer cells in ER(+) tumors. Difficulties in accessing fertility preservation procedures were mainly due to patients' reluctance, but also to lack of coordination with the assisted reproduction specialists. No full consensus was reached on the prognostic role of pregnancy after BCa. Fifty-four percent of oncologists declared that pregnancy does not affect oncologic prognosis. Treatment with GnRHa during chemotherapy was considered the only mean for preserving ovarian function.Fertility preservation in BCa patients is a well-accepted practice among Italian oncologists. A poor knowledge of this specific issue emerged from the survey, even if a certain degree of agreement was observed on most fertility-related issues.

Epithelial ovarian cancer is often considered a single pathological entity, but increasing evidence suggests that it is rather a group of different neoplasms, each with unique pathological characteristics, molecular features, and clinical behaviours. This heterogeneity accounts for the different sensitivity to antineoplastic drugs and makes the treatment of ovarian tumours a challenge. For early-stage disease, as well as for heavily pre-treated patients with recurrent ovarian cancer, the benefit of chemotherapy remains uncertain. Clear-cell, mucinous, low-grade serous, and endometrioid carcinomas show different molecular characteristics, which require different therapeutic approaches. In the era of personalised cancer medicine, understanding the pathogenesis and the genetic background of each subtype of epithelial ovarian tumour may lead to a tailored therapy, maximising the benefits of specific treatments and possibly reducing the side effects. Furthermore, personal factors, such as the patient’s performance status, should be taken into account in the management of ovarian cancer, with the aim of safeguarding the patients’ quality of life.

Purpose of the study A retrospective analysis on 1407 patients with invasive ductal carcinoma (IDC) and 243 invasive lobular carcinoma (ILC) was performed in order to compare the histological features, the immunohistochemical characteristics, the surgical treatment and the clinical outcome in the two groups. Results ILC seems to be more likely multifocal, estrogen receptor positive, HER-2 negative and to have a lower proliferative index compared to IDC. ILC, when treated with conservative surgery, required more frequently re-excision and/or mastectomy because of positive resection margins. No difference was observed in terms of 5-year disease free survival and local relapse free survival between the two groups, in the whole series and in the subgroup of patients treated with breast-conserving treatment. Conclusion ILC can be safely treated with conservative surgery but a more accurate preoperative evaluation of tumor size and multifocality could be advocated, in order to reduce the re-excision rate.