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

Ovarian cancer in BRCA1 and BRCA2 gene mutation carriers: Analysis of prognostic factors and survival

OBJECTIVES: To compare clinical–pathological characteristics and outcome between sporadic ovarian cancer and ovarian cancer in patents with hereditary breast and ovarian cancer syndrome (HBOC). METHODS: Twenty-four patients with ovarian cancer treated between 2000 and 2009 who tested positive for BRCA1/2 mutation (BRCA+) and a control group of 64 age-matched patients with no family history of breast/ovarian cancer (controls) were enrolled. Clinical–pathological characteristics, surgical outcome, overall (OS), and progression-free survival (PFS) were compared between the two groups. RESULTS: The high-grade serous histotype was more represented in BRCA+ than in controls (70.8% versus 53.1%) (p > 0.05). BRCA+ cancers were more frequently diagnosed at stage II than controls (20.83% versus 4.69%) (p = 0.024). Radical primary surgery was performed in 70% of women in both groups, with no difference in debulking results. In patients undergoing surgery after neoadjuvant chemotherapy, in all BRCA+ patients, optimal cytoreduction was achieved (versus 70% of the controls). PFS was significantly longer for BRCA+ patients compared to controls (60 months versus 22 months; p = 0.039). No significant difference was observed in OS between BRCA+ patients and controls. CONCLUSIONS: At a median follow-up time of 46 months, BRCA+ patients have a better prognosis than controls in terms of PFS. Higher chemosensitivity of BRCA+ tumours was observed

Accelerated partial breast irradiation using 3D conformal radiotherapy: Toxicity and cosmetic outcome

Purpose: The aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Methods and materials: 84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five nocoplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The doseevolume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale. Results: Median patient age was 66 years (range 51e87). Median follow-up was 36.5 months (range 13 e83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p ¼ 0.33) or irradiated volume (p ¼ 0.45). Conclusions: APBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse

Cytoreductive Surgery for Heavily Pre-Treated, Platinum-Resistant Epithelial Ovarian Carcinoma: A Two-Center Retrospective Experience

Few retrospective studies have shown a benefit in selected patients affected by heavily pre-treated, platinum-resistant ovarian carcinomas (PROCs) who have undergone cytoreduction at relapse. However, the role of tertiary and quaternary cytoreductive surgery is not fully defined. Our aim was to evaluate survival and surgical morbidity and mortality after maximal cytoreduction in this setting. We evaluated all consecutive patients undergoing cytoreduction for platinum-resistance over an 8-year period (2010–2018) in two different centers. Fifty patients (median age 52.5 years, range 34–75) were included; the median number of previous chemotherapy lines was three (range 1–7) and the median number of previous surgeries was one (range 1–4). Completeness of cytoreduction (CC = 0) was achieved in 22 patients (44%). Rates of major operative morbidity and 30-day mortality were 38% and 8%, respectively. Median follow-up was 35 months. The absence of tumor residual (CC = 0) was associated with a significantly better overall survival (OS) compared to the CC > 0 subgroup (median OS 32.9 months (95% CI 21.6–44.2) vs. 4.8 months (95% CI n.a.–9.8), hazard ratio (HR) 4.21 (95% CI 2.07–8.60), p < 0.001). Optimal cytoreduction is feasible and associated with promising OS in selected, heavily pre-treated PROCs. Further prospective studies are required to better define the role of surgery in platinum-resistant disease

Effects of Surgical and Adjuvant Therapies for Breast Cancer on Sexuality, Cognitive Functions, and Body Weightj sm_1725 1891..1900

Introduction. Breast cancer and its treatment negatively affect the important aspects of a woman's life such as sexual health, cognitive functions, body image, and weight. Abrupt estrogen deficiency following chemotherapy and/or hormonal therapy plays an important role in worsening of sexuality. Aim. To evaluate the impact of breast cancer treatment on sexual functioning, cognitive function, and body weight in premenopausal women. Methods. Thirty-five women with a premenopausal diagnosis of breast cancer who are candidate to adjuvant treatment completed validated questionnaires on menopausal symptoms, sexuality, partner relationship, depression, body image, and cognitive functions after surgery (T0), then after chemotherapy or at least 6 months of endocrine therapy (T1), and after 1 year (T2). In addition, gynecological and dietological examinations were performed. Main Outcome Measure. The following validated questionnaires were used: Greene Climacteric Scale, Beck Depression Inventory, Body Attitude Test, McCoy revised Italian version McCoy Female Sexuality Questionnaire, Cues for Sexual Desire Scale, Dyadic Adjustment Scale, Numeric Matrix Test and Rey uditory-verbal learning test, to measure cognitive functions, a recall 24 H questionnaire to evaluate food intake, Minnesota Leisure Time Physical Activity questionnaire and Eating Attitude Test-40, while anthropometric and plicometry data were assessed by a dietitian. Results. Low levels of sexual functioning were registered at baseline; a further decrease in sexual activity, quality of the partnered relationship, desire, and arousability was demonstrated at T1 and T2. We found a significant increase in hot flushes and anxiety. Nonsignificant deterioration of body image was demonstrated. Although women reported losing memory and concentration, "chemobrain" effect was not demonstrated as cognitive tests improved after 6 months, probably because of "learning effect." Women who had undergone chemotherapy gained weight and fat disposition was typically android. Conclusions. Young women undergoing adjuvant breast cancer therapy experience a heavy impairment in important quality of life domains as sexuality and targeted support interventions are needed. Biglia N, Moggio G, Peano E, Sgandurra P, Ponzone R, Nappi RE, and Sismondi P. Effects of surgical and adjuvant therapies for breast cancer on sexuality, cognitive functions and body weight

The impact of malignant nipple discharge cytology (NDc) in surgical management of breast cancer patients

BACKGROUND: The role of nipple discharge cytology (NDc) in the surgical management of breast cancer patients is unclear. We aimed: (i) to evaluate the effect of malignant NDc on the surgical approach to the nipple-areola complex, and (ii) to verify the association between malignant NDc and nipple malignancy. METHODS: We retrospectively analyzed a case series of 139 patients with NDc who underwent breast surgery. The clinical and histological findings, types of surgery with emphasis on nipple-areola complex amputation, immunohistochemical phenotypes of the carcinomas and measurements of the tumor-nipple distance were recorded. Additionally, in patients who showed HER2-positive lesions on definitive surgery, we evaluated the HER2 immunocytochemistry of the NDc smears. RESULTS: Thirty-two malignant and 107 benign/borderline NDc diagnoses were identified. All 32 malignant-NDc cases were histologically confirmed as malignant. Thirty borderline/benign-NDc cases were histologically diagnosed as malignant (sensitivity 58%). The majority of the patients with malignant NDc were treated with nipple-areola complex amputations in both the mastectomy and conservative surgery groups (P<0.001, chi251.77). Nipple involvement was strongly associated with HER2-positive ductal carcinoma in-situ (P<0.001, chi211.98). HER2 immunocytochemistry on the NDc revealed a 100% correlation with the immunocytochemistry performed on the surgical tissues. CONCLUSIONS: Malignant NDc influenced surgical management. The association of malignant NDc with nipple involvement is highly related to ductal carcinoma in-situ with HER2 overexpression. In case of HER2 positive NDc, nipple-areola complex involvement is more likely than in HER2 negative cases

PIK3R1W624R Is an Actionable Mutation in High Grade Serous Ovarian Carcinoma.

Identifying cancer drivers and actionable mutations is critical for precision oncology. In epithelial ovarian cancer (EOC) the majority of mutations lack biological or clinical validation. We fully characterized 43 lines of Patient-Derived Xenografts (PDXs) and performed copy number analysis and whole exome sequencing of 12 lines derived from naïve, high grade EOCs. Pyrosequencing allowed quantifying mutations in the source tumours. Drug response was assayed on PDX Derived Tumour Cells (PDTCs) and in vivo on PDXs. We identified a PIK3R1W624R variant in PDXs from a high grade serous EOC. Allele frequencies of PIK3R1W624R in all the passaged PDXs and in samples of the source tumour suggested that it was truncal and thus possibly a driver mutation. After inconclusive results in silico analyses, PDTCs and PDXs allowed the showing actionability of PIK3R1W624R and addiction of PIK3R1W624R carrying cells to inhibitors of the PI3K/AKT/mTOR pathway. It is noteworthy that PIK3R1 encodes the p85α regulatory subunit of PI3K, that is very rarely mutated in EOC. The PIK3R1W624R mutation is located in the cSH2 domain of the p85α that has never been involved in oncogenesis. These data show that patient-derived models are irreplaceable in their role of unveiling unpredicted driver and actionable variants in advanced ovarian cancer