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Neoadjuvant chemotherapy (NAC) is an established treatment option for early breast cancer, potentially downstaging the tumor and increasing the eligibility for breast-conserving surgery (BCS). The primary aim of this study was to assess the rate of BCS after NAC, and the secondary aim was to identify predictors of application of BCS after NAC. This was an observational prospective cohort study of 226 patients in the SCAN-B (Clinical Trials NCT02306096) neoadjuvant cohort during 2014–2019. Eligibility for BCS was assessed at baseline and after NAC. Uni- and multivariable logistic regression analyses were performed using covariates with clinical relevance and/or those associated with outcome (BCS versus mastectomy), including tumor subtype, by gene expression analysis. The overall BCS rate was 52%, and this rate increased during the study period (from 37% to 52%). Pathological complete response was achieved in 69 patients (30%). Predictors for BCS were smaller tumor size on mammography, visibility on ultrasound, histological subtype other than lobular, benign axillary status, and a diagnosis of triple-negative or HER2-positive subtype, with a similar trend for gene expression subtypes. Mammographic density was negatively related to BCS in a dose-response pattern. In the multivariable logistic regression model, tumor stage at diagnosis and mammographic density showed the strongest association with BCS. The rate of BCS after NAC increased during the study period to 52%. With modern treatment options for NAC the potential for tumor response and BCS eligibility might further increase. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To survey the histopathological abnormalities in breasts of women who have undergone risk reducing mastectomy and to evaluate the effect of this measure on future breast cancer development. Patients/methods: Between August 1995 and October 2006 100 consecutive women with a hereditary increased risk of breast cancer underwent prophylactic mastectomy (PM) at Malmö University Hospital. Fifty of the 100 women had no previous breast cancer. Fifty were BRCA1 or BRCA2 mutation carriers. All breast specimens have been examined histopathologically according to a prospective protocol. Follow-up data was collected from medical records and data in the Regional Cancer Registry. Results: In the PM specimens abnormal lesions were found in 18 women (three with invasive cancers, eight in situ cancers and seven atypical hyperplasia). In previously healthy women lesions were more frequent after the age of 40 than among younger women (p =0.03). BRCA mutation carriers were more likely to present with ADH (atypical ductal hyperplasia)/ALH (atypical lobular hyperplasia) compared to the non-carriers/untested cases (p =0.01). After a median follow-up of 52 months (range 1–136 months) none of the women have developed breast cancer in the area of the prophylactically removed breast. Conclusions: Prevalent atypical or malignant lesions are relatively a common finding in PM specimens in asymptomatic women with hereditary increased risk of breast cancer. Such findings were significantly more common above age 40 in women without previous breast cancer. The risk of newly formed breast cancer after PM is small. The clinical importance of detecting a premalignant or preinvasive lesion in the breast at PM is still unclear. [Copyright &y& Elsevier]

Summary: Prophylactic mastectomy is an effective risk-reducing option in women with hereditary increased risk of breast cancer. It may be combined with immediate reconstruction, with the intention of improving aesthetic outcome and health-related quality of life. Sixty-one women underwent prophylactic mastectomy and immediate breast reconstruction in Malmö, Sweden, between 1995 and 2003. Forty women underwent bilateral prophylactic mastectomy and immediate reconstruction. Ten of these had a previous breast cancer diagnosis. Twenty-one women underwent contralateral prophylactic mastectomy and immediate reconstruction after a previous breast cancer. Fifty-four of the women (89%) were evaluated clinically for aesthetic results and complications. Patient satisfaction and quality of life were evaluated with one study-specific and two standardised health-related questionnaires administered at time of clinical follow-up. Median follow-up time was 42 months (range 7–99 months). The position of the reconstructed breasts was judged as satisfactory in 77% of breasts. Symmetry in relation to the midline was adequate in 89% of breasts. A capsular contracture grade III according to Baker and indentation tonometry was observed in 1% of breasts (1/104). The complication rate was 18% (7% early and 11% late). Secondary corrections were carried out in 11% of breasts. The study-specific questionnaire revealed a high degree of satisfaction. No woman regretted the procedure, and all women would have chosen the same type of surgery again. An age-stratified comparison of Swedish women using the Short Form 36 Health Survey Questionnaire (SF-36) questionnaire was carried out for this study. The study population scores were high, suggesting that prophylactic mastectomy and immediate reconstruction on both physical and psychological issues in this retrospective study had no negative effect. Also, the Hospital Anxiety and Depression Scale (HAD) questionnaire did not suggest any increased anxiety or depression among the patients. Prophylactic mastectomy and immediate breast reconstruction in women at risk of hereditary breast cancer may be carried out with a satisfactory aesthetic outcome and an acceptable rate of complications comparable to those in other studies, and does not in itself seem to be associated with a decreased quality of life. [Copyright &y& Elsevier]

Background: A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear. Patients and methods: Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden. Results: Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years). Conclusions: In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ~1/3 and germline 2/3. This may have implications for treatment and genetic counseling. [ABSTRACT FROM AUTHOR]

An enhanced understanding of the biology of breast cancer metastases is needed to individualize patient management. Here, we show that tumor characteristics of breast cancer metastases significantly influence post-relapse survival, emphasizing that molecular investigation at relapse offers clinically relevant information, with the potential to improve patient management and survival.Background We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. Patients and methods The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and β-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. Results A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and β-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3–10.9] and HER2-enriched (HR 4.4; 95% CI 1.5–12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. Conclusions We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information. ClinicalTrials.gov This is the translational part of the Swedish multicenter and randomized trial TEX, clinicaltrials.gov identifier nct01433614 (http://www.clinicaltrials.gov/ct2/show/nct01433614). [ABSTRACT FROM PUBLISHER]

At least 10% of all ovarian cancers are estimated to have a hereditary background. Hereditary breast–ovarian cancer (HBOC) due to mutations in the BRCA genes is a major cause of hereditary ovarian cancer, although its frequency and relationship to age and family history in unselected series of ovarian cancers is not completely known. We report here the results of a full mutational screening analysis for germ line BRCA1 and BRCA2 mutations in 161 patients with invasive epithelial ovarian carcinomas. Age at diagnosis ranged from 22 to 82 years (mean 59 years). Deleterious (frame-shift, nonsense and missense) mutations were detected in 13/161 (8%) of the patients and affected BRCA1 in 12 cases and BRCA2 in one case. Four additional missense variants (one in BRCA1 and three in BRCA2) with a possible association with an increased risk ovarian cancer were revealed, resulting in a total frequency of BRCA gene alterations of 17/161 (11%). The 13 patients with deleterious mutations had a mean age of 57 years (range 41–76 years) and only three of these patients were below 50 years of age. A family history of at least one breast cancer and/or ovarian cancer was reported in all but 1 of the patients with BRCA mutations compared with only 24% of patients without mutations. Our findings in this prospective study confirm approximately 1 in 10 patients with ovarian cancer carry a germ line BRCA gene mutation associated with HBOC, and also indicate that a large number of these patients are over 50 years of age at diagnosis. [Copyright &y& Elsevier]