Positive Nipple Margins in Nipple-Sparing Mastectomy: Management of Nipples Containing Cancer or Atypia.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe approach for breast cancer treatment and prevention; however, there are little long-term data to guide management for patients whose nipple margins contain tumor or atypia. METHODS: NSM patients with tumor or atypia in their nipple margin were identified from a prospectively maintained, single-institution database of consecutive NSMs. Patient and tumor characteristics, treatment, recurrence, and survival data were assessed. RESULTS: A total of 3158 NSMs were performed from June 2007 to August 2019. Nipple margins contained tumor in 117 (3.7%) NSMs and atypia only in 164 (5.2%) NSMs. Among 117 nipple margins that contained tumor, 34 (29%) margins contained invasive cancer, 80 (68%) contained ductal carcinoma in situ only, and 3 (3%) contained lymphatic vessel invasion only. Management included nipple-only excision in 67 (57%) breasts, nipple-areola complex excision in 35 (30%) breasts, and no excision in 15 (13%) breasts. Only 23 (24%) excised nipples contained residual tumor. At 67 months median follow-up, there were 2 (1.8%) recurrences in areolar or peri-areolar skin, both in patients with nipple-only excision. Among 164 nipple margins containing only atypia, 154 (94%) nipples were retained. At 60 months median follow-up, no patient with atypia alone had a nipple or areola recurrence. CONCLUSIONS: Nipple excision is effective management for nipple margins containing tumor. No intervention is required for nipple margins containing only atypia. Our results support broad eligibility for NSM with careful nipple margin assessment.

Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Evaluation of Anti-Mullerian Hormone Levels, Antral Follicle Counts, and Mean Ovarian Volumes in Chemotherapy-Induced Amenorrhea among Breast Cancer Patients: A Prospective Clinical Study.

Estradiol (E2), a follicle-stimulating hormone (FSH), AMH, and inhibin B levels, along with AFC and MOV, are used to determine ovarian reserve in pre-menopausal women. Studies have shown that AMH levels are more sensitive than those of E2, FSH, and inhibin B and that AFC and MOV can be used to evaluate ovarian reserve. AMH, AFC, and MOV measurements were performed before and after adjuvant SC in 3-month periods for one year. Patients were classified as experiencing chemotherapy-induced amenorrhea (CIA) if they did not have menstrual cycles for a period of six months or longer following the conclusion of their chemotherapy treatment. We aimed to evaluate the factors affecting chemotherapy-induced amenorrhea in breast cancer patients treated with adjuvant chemotherapy and the performance of baseline measurements of AMH, AFC, and MOV to predict chemotherapy-induced amenorrhea. The effects of different chemotherapy regimens on the AMH level, AFC, and MOV in CIA patients were investigated. Seventy-one patients were eligible for this study, and the median age was 38 years (range: 23-45). The median follow-up was 37 months (range: 20-51), and CIA developed in 62% of the patients. The AMH level and AFC were significantly decreased one year after SC (p < 0.0001), whereas MOV was not (p = 0.507). AMH levels before chemotherapy (median: 1.520 vs. 0.755, p = 0.001) and at the end of the first year (median: 0.073 vs. 0.010, p = 0.030) and pre-treatment AFC (median: 12 vs. 4.50, p = 0.026) were lower in patients with CIA compared to those without CIA. The AMH levels before SC were the most valuable and earliest factor for predicting CIA development. In addition, there was no difference between the chemotherapy regimens (including or not including taxane) in terms of CIA development.

Assessment High-Risk Breast Cancer in Older Patients: A Comparative Analysis of PREDICT Scores and TAILORx Risk Categorization.

Objective: This study aimed to evaluate the relationship between PREDICT tool overall survival (OS) scores and high-risk patients according to TAILORx risk categorization in elderly hormone reseptor (HR) positive human epidermal growth factor negative early breast-cancer patients. Materials and Methods: We conducted a retrospective study, extracting data from medical records of 64 patients diagnosed with breast cancer. A retrospective analysis was performed on all patients who had Oncotype Dx Recurrence Scores across five medical centers between 2017 and 2022. PREDICT scores were defined as calculated 10-year OS rates via PREDICT tool. Results: The median age of the patients was 67, with a range between 65-75 years. Low-risk patients had a slightly higher two PREDICT scores compared to high-risk patients (78% vs. 73%), (81% vs. 77%), which were statistically significant. The progesterone receptor (PR) level was significantly lower in the high-risk group (3.5% vs. 80%). A unit decrease in the PREDICT scores was associated with a 11% increase in the odds of being in the high-risk group. However, these effects weren't statistically significant in the multivariate analysis. A unit decrease in the PR level was significantly associated with increased odds (by 5% in the multivariate analysis) of being in the high-risk group. Conclusion: Our study underscores the importance of using a combination of tools, including the PREDICT tool, PR levels, and TAILORx risk categorization, for a comprehensive risk assessment in these patients, especially in the older population. Accurate risk assessment is crucial for tailoring the treatment and optimizing outcomes in this vulnerable population. Future studies are warranted to further validate these findings in larger cohorts and to explore additional biomarkers and genomic signatures that may aid in the risk assessment and management of breast cancer in older patients.

MCM-2 Levels as a Potential Biomarker for Predicting High-Risk Breast Cancer Patients According to TAILORx Classification.

Background: The minichromosome maintenance protein-2 (MCM-2) is a more sensitive proliferation marker than Ki-67. This study aimed to evaluate the relationship between MCM-2 and Oncotype DX recurrence score (ODX-RS) and determine an MCM-2 cutoff value in high-risk patients according to TAILORx risk categorization. Methods: Hormone receptor (HR) positive HER-2 negative early-stage breast cancer patients (pT1-2, pN0-N1, M0) who had ODX-RS were included in the study. According to the TAILORx trial, patients were divided into two groups with high (ODX-RS ≥26) and low risk (ODX-RS <26) in terms of ODX-RS. Formalin-fixed-paraffin-embedded tissues of patients were re-evaluated, and 3 µm sections were prepared for MCM-2 immuno-histochemical staining. The relationship between ODX-RS and the percentage of MCM-2 staining was evaluated in two groups. The ROC curve analysis was performed to determine the MCM-2 cut-off value for the TAILORx high-risk group (ODX-RS ≥26). Results: The mean MCM-2 value was significantly higher in the high-risk group [(60.2 ± 11.2 vs 34.4 ± 13.8, p < 0.001)]. In the multivariate analysis, MCM-2 (OR: 1.27, 95% CI: 1.08-1.49, p = 0.003) and progesterone receptor (PR) levels ≤10% (OR: 60.9, 95% CI: 4.1-89.7, p = 0.003) were found to be independent factors indicating a high-risk group. A one-unit increase in MCM-2 level increased the likelihood of being in the high-risk group by 1.27 times. In the ROC curve analysis, the optimal MCM-2 cut-off level was 50 (AUC: 0.921, sensitivity: 86.7%, specificity: 96.0%, p < 0.001). Conclusion: Our study is the first study in the literature to investigate the relationship between ODX-RS and MCM-2 levels in HR-positive HER-2 negative early breast-cancer patients. In this study, MCM-2 was an independent risk factor in identifying high-risk patients according to TAILORx risk classification. MCM 2 cut-off value (50) may help the decision on adjuvant chemotherapy in patients where the Oncotype DX test cannot be performed.

Conformable ultrasound breast patch for deep tissue scanning and imaging.

Ultrasound is widely used for tissue imaging such as breast cancer diagnosis; however, fundamental challenges limit its integration with wearable technologies, namely, imaging over large-area curvilinear organs. We introduced a wearable, conformable ultrasound breast patch (cUSBr-Patch) that enables standardized and reproducible image acquisition over the entire breast with less reliance on operator training and applied transducer compression. A nature-inspired honeycomb-shaped patch combined with a phased array is guided by an easy-to-operate tracker that provides for large-area, deep scanning, and multiangle breast imaging capability. The in vitro studies and clinical trials reveal that the array using a piezoelectric crystal [Yb/Bi-Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3] (Yb/Bi-PIN-PMN-PT) exhibits a sufficient contrast resolution (~3 dB) and axial/lateral resolutions of 0.25/1.0 mm at 30 mm depth, allowing the observation of small cysts (~0.3 cm) in the breast. This research develops a first-of-its-kind ultrasound technology for breast tissue scanning and imaging that offers a noninvasive method for tracking real-time dynamic changes of soft tissue.

Survival results according to Oncotype Dx recurrence score in patients with hormone receptor positive HER-2 negative early-stage breast cancer: first multicenter Oncotype Dx recurrence score survival data of Turkey.

Background: The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions. Patients and methods: Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS. Results: A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18. Conclusion: This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.

Treatment Changes in Breast Cancer Management and De-Escalation of Breast Surgery.

A better understanding of tumor biology and new drugs have led to significant changes in the management of breast cancer (BC). Radical mastectomy, which had been the treatment for BC for more than a century, was based on the hypothesis that BC is a local-regional disease. In the 1970s, Fisher's studies showed that cancer cells could reach the systemic circulation without passage through the regional lymphatic system. Multidisciplinary treatment of BC, which was now considered a systemic disease, was started and radical mastectomy was replaced by breast-conserving surgery (BCS)+, axillary dissection (AD), systemic chemotherapy, hormonotherapy, and radiotherapy in early-stage BC. Modified radical mastectomy, chemotherapy, and radiotherapy were applied as a treatment for locally advanced BC. However, later clinical studies demonstrated that the breast can be preserved in those who respond well to neo-adjuvant chemotherapy (NAC). In the early 1990s, sentinel lymph node biopsy (SLNB) in early-stage BC (cN0) was performed using blue dye and radioisotope markers. It was shown that AD may be avoided in SLN-negative patients, and SLNB has been a standard intervention in cN0 patients. In this way, the very serious complications of AD, especially lymphedema, were avoided. BC has been shown to be a heterogeneous disease and the tumor may be divided into four different molecular subtypes. Thus, optimal treatment differed from patient to patient (one size fits all was inappropriate), individualized treatments have emerged and over-treatment was avoided. The prolongation of life expectancy and the decrease in recurrence led to an increase in the rate of BCS, an acceptable cosmetic result with oncoplastic surgery, and a better quality of life. The increase in the rate of complete response to NAC with new and targeted agents and especially in human epidermal growth factor receptor-2+ and triple-negative patients with a poor prognosis has led to the use of NAC regardless of cN0. The complete disappearance of the tumor after NAC has been reported by some studies, suggesting that breast surgery may not be needed. However, other studies have shown that vacuum biopsies performed on the tumor bed have a high rate of false negativity. Therefore, it is difficult to suggest that there is no need for lumpectomy, which is cheaper and safer today. The false negativity rate of SLNB is high in patients with cN1 at the time of diagnosis and cN0 after NAC (approximately 13%). In order to reduce this rate to ≤5%, clinical studies have recommended the use of the dual method, marking the positive lymph node before chemotherapy and removing 3-4 nodules with SLN. In summary, a better understanding of tumor biology and new drugs have changed the management of BC and de-escalate the role of surgical treatment.

Current Challenges and Perspectives in Breast Cancer in Elderly Women: The Senologic International Society (SIS) Survey.

Objective: Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives. Materials and Methods: The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives. Results: Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials. Conclusion: Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.

Molecular Signatures in Ductal Carcinoma In Situ (DCIS): A Systematic Review and Meta-Analysis.

CONTEXT: Adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is debated as benefits are inconstant. Molecular signatures for DCIS have been developed to stratify the risk of local recurrence (LR) and therefore guide the decision of RT. OBJECTIVE: To evaluate, in women with DCIS treated by BCS, the impact of adjuvant RT on LR according to the molecular signature risk stratification. METHODOLOGY: We conducted a systematic review and meta-analysis of five articles including women with DCIS treated by BCS and with a molecular assay performed to stratify the risk, comparing the effect of BCS and RT versus BCS alone on LR including ipsilateral invasive (InvBE) and total breast events (TotBE). RESULTS: The meta-analysis included 3478 women and evaluated two molecular signatures: Oncotype Dx DCIS (prognostic of LR), and DCISionRT (prognostic of LR and predictive of RT benefit). For DCISionRT, in the high-risk group, the pooled hazard ratio of BCS + RT versus BCS was 0.39 (95%CI 0.20-0.77) for InvBE and 0.34 (95%CI 0.22-0.52) for TotBE. In the low-risk group, the pooled hazard ratio of BCS + RT versus BCS was significant for TotBE at 0.62 (95%CI 0.39-0.99); however, it was not significant for InvBE (HR = 0.58 (95%CI 0.25-1.32)), Discussion: Molecular signatures are able to discriminate high- and low-risk women, high-risk ones having a significant benefit of RT in the reduction of invasive and in situ local recurrences, while in low-risk ones RT did not have a benefit for preventing invasive breast recurrence. The risk prediction of molecular signatures is independent of other risk stratification tools developed in DCIS, and have a tendency toward RT de-escalation. Further studies are needed to assess the impact on mortality.

Is Breast Conserving Surgery Efficacious in Breast Cancer Patients with BRCA1 or BRCA2 Germline Mutation?

Background: The optimal surgical therapy for newly diagnosed breast cancer with germline mutations in susceptibility genes is still uncertain for many physicians. In this study, we aimed to determine the efficacy of breast conserving surgery (BCS) in breast cancer patients with BRCA1 or BRCA2 mutation by assessing its outcomes and locoregional recurrence (LR) rates. Materials and Methods: Seventy-five patients operated with BCS or mastectomy for breast cancer between 2006 and 2017 and had BRCA1 or BRCA2 mutation were included in the study. Effects of the performed breast surgery and clinicopathological characteristics on surgical outcomes, LR rates and survival were analyzed with showing the distribution of BRCA1 and BRCA2 germline mutations. Results: The median age of the patients was 42 years (20-77). BRCA1 mutations were found in 46 (61.3%) patients and BRCA2 mutations in 29 (38.7%) patients. Compared to BRCA2 carriers, BRCA1 carriers were more likely to have higher tumor grade (84.8% vs 44.8%; p = 0.001) and non-luminal subtype tumors (67.4% vs 13.8%; p = 0.001). A total of 44 (58.7%) patients underwent unilateral mastectomy and 31 (41.3%) patients underwent BCS. At a median follow-up time of 60 (12-240) months, LR was observed in 6 patients equally divided in both BCS and mastectomy groups. LR rates were slightly higher after BCS versus mastectomy (9.7% and 6.8%, respectively). Additionally, there were no statistically significant differences in disease-free survival (DFS) and disease-specific survival (DSS) rates after 10 years in the BCS group versus the mastectomy group (p = 0.117 and 0.109, respectively), but in fact, the rates were better in the BCS group. Conclusion: Our findings indicate that BCS may serve as an efficacious alternative to mastectomy for breast cancer patients with BRCA1 or BRCA2 mutation. Additionally, tumor size, lymph node positivity, and TNM stage should be taken into consideration for a better surgical decision-making.

The Senologic International Society Survey on Ductal Carcinoma In Situ: Present and Future.

Objective: Therapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among countries worldwide, and some treatment indications are still controversial. To investigate DCIS management in different countries; identify both consensual practices and controversial topics; and survey opinions about the future management of DCIS. Materials and Methods: The Senologic International Society network members participated to an online survey using a questionnaire, between November 2021 and February 2022. Results: Twenty-two responses from 20 different countries showed that organized breast cancer screening programs were present for 87% participants, and DCIS cases represented 13.7% of all breast cancers. Most participants used the grade classification (100%), the morphological classification (78%) and performed immunohistochemistry assays (73%). In case of conservative treatment, the mean re-excision rate was 10.3% and clear margins of mean 2.5 mm were considered healthy. Radical mastectomy rate was 35.5% with a breast reconstruction rate of 53%. Tumor bed boost indications were heterogeneous, and 73% of participants indicated hormone therapy for hormone-positive DCIS. Surgery and radiotherapy omission for some low-risk DCIS were considered by 73% of participants. Multigene assays were used by 43% of participants. Concerning future changes in DCIS management, participants mostly answered surgical de-escalation (48%), radiotherapy de-escalation (35) and/or active surveillance for some cases (22%). Conclusion: This survey provided an overview of the current practices of DCIS management worldwide. It showed that some areas are rather consensual: incidence increases over time, treatment in young women, pathological classifications, definition of healthy margins, the skin-sparing mastectomy and immediate breast reconstruction. However, some topics are still debated and result in heterogeneous practices, such as evolution in the age of diagnosis, the benefit of de-escalation in low-risk DCIS among elderly women, indications for hormone therapy, radiotherapy omission, or multigene assays. Further evidence is needed to reach consensus on these points, and innovative approaches are still under evaluation in clinical trials. The International Senologic Society, by its members, encourages precision medicine and personalized treatments for DCIS, to avoid overtreatment and overdiagnosis, and provide better healthcare to women with DCIS.

Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) for the prevention of breast cancer-related lymphedema after axillary lymph node dissection using bioimpedance spectroscopy.

BACKGROUND: Lymphedema is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 20%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of lymphedema dramatically. Our initial study showed an 88% decrease in clinical lymphedema rate. In the initial study, we used arm circumference measurement for the diagnosis of lymphedema and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting lymphedema. STUDY DESIGN: All patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (±10 L-Dex unit) or ≥10 L-Dex unit increase above patient's baseline was considered as lymphedema. The incidence of lymphedema was compared between patients with and without SLYMPHA. RESULTS: 194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ± 37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of lymphedema (16% vs 32%; p = 0.01; OR 0.4 [0.2-0.8]). CONCLUSION: SLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.

Axillary Response to Neoadjuvant Therapy in Node-Positive, Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: Predictors and Oncologic Outcomes.

BACKGROUND: One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) patients is axillary downstaging to avoid axillary dissection. OBJECTIVE: The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response. METHODS: A prospectively collected database was queried for node-positive, ER+, HER2- breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model. RESULTS: A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p = 0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p = 0.03). NET patients with ypN0 were younger and were treated for a longer period of time (>6 months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR. CONCLUSIONS: For patients with node-positive, ER+, HER2- breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response.

Importance of multigene panel test in patients with consanguineous marriage and family history of breast cancer.

Next-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer-related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2% in BRCA1/2 genes; 6, 24, and 14% in other high, moderate and low-risk genes, respectively. The CM rate was 17.7% among the 215 patients with BC. The PV rate was 13.2% in patients with CM and 16.4% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3%, P=0.045). Analysis of multigene panel provided 9.76% additional PVs in moderate/low-risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.

Comparison of breast cancer patients who underwent partial mastectomy (PM) with mini latissimus dorsi flap (MLDF) and subcutaneous mastectomy with implant (M + I) regarding quality of life (QOL), cosmetic outcome and survival rates.

PURPOSE: The latissimus dorsi muscle has long been used in breast cancer (BC) patients for reconstruction. This study aimed to compare early stage BC patients who had partial mastectomy (PM) with mini latissimus dorsi flap (MLDF) and subcutaneous mastectomy with implant (MI) with respect to quality of life (QoL), cosmetic outcome (CO), and survival rates. PATIENTS AND METHODS: The data of patients who underwent PM + MLDF (Group 1) and M + I (Group 2) between January 2010 and January 2018 were evaluated. Both groups were compared in terms of demographics, clinical and pathological characteristics, surgical morbidity, survival, quality of life, and cosmetic results. The EORTC-QLQ C30 and EORTC-QLO BR23 questionnaires and the Japanese Breast Cancer Society (JBCS) Cosmetic Evaluation Scale were used to assess the quality of life and the cosmetic outcome, respectively. RESULTS: A total of 317 patients were included in the study, 242 (76.3%) of them in group 1 and 75 (23.6%) of them in group 2. Median follow-up time was 56 (14-116) months. There were no differences identified between the groups in terms of tumor histology, hormonal receptors and HER-2 positivity, surgical morbidity, and 5-year overall and disease-free survival. Group 2 patients were significantly younger than group 1 (p = 0.003). The multifocality/multicentricity rate was higher in group 2 (p ≤ 0.001), whereas tumor size (p = 0.009), body mass index (BMI, p = 0.006), histological grade (p ≤ 0.001), lymph node positivity (p = 0.002), axillary lymph node dissection (ALND) rate (p = 0.005), and presence of lympho-vascular invasion (LVI, p = 0.013) were significantly higher in group 1. When the quality of life was assessed by using the EORTC QLQ C30 and BR23 questionnaires, it was seen that the body image perception (p < 0.001) and nausea/vomiting score (p = 0.024) were significantly better in PM + MLDF group whereas physical function score was significantly better in M + I group (p = 0.012). When both groups were examined in terms of cosmesis with JBCS Cosmetic Evaluation Scale, good cosmetic evaluation score was significantly higher in patients in MLDF group (p = 0.01). DISCUSSION: The results of this study indicate that in comparison to M + I procedure, the PM + MLDF procedure provides significantly superior results in terms of body image and cosmetic result with similar morbidity and oncologic outcomes. In selected patients with small breasts and a high tumor/breast ratio, PM + MLDF may be an alternative to subcutaneous mastectomy and implant.

The Impact of Advanced Image-Guided Breast Surgery and Oncoplastic Techniques on Margin Positivity in Breast Conserving Surgery.

Objective  Positive margins remain a significant psychological and economic burden after breast conserving surgery. The aim of this study was to test the hypothesis that advanced oncoplastic techniques as well as intraoperative integrative imaging with intraoperative ultrasound and mobile digital specimen radiography decreases positive margin rate in breast conserving surgery. Methods  A single-institution retrospective review of a prospectively collected database was performed. Patients with breast neoplasms who underwent lumpectomy with or without using intraoperative integrative imaging approaches and oncoplastic techniques were included. The primary outcome was positive margin rate for each technique. Results  A total of 392 patients were included in the study. The median age of the cohort was 59 years. Overall positive margin rate was 15%. Ductal carcinoma in situ (DCIS) histology and larger tumor size were associated with higher positive margin rate. Intraoperative integrative imaging significantly decreased positive margin rate (9% vs. 18%, p=0.018). Oncoplastic techniques also decreased positive margin rate from 16% to 12%, however this was not significant. Conclusion  Positive margin rate was significantly lower when intraoperative integrative imaging was used. Oncoplastic techniques also decreased positive margin rate in a selected group of patients with large tumor size. We suggest incorporating these techniques in all breast conserving surgery cases.

Lymph Node Ratio (LNR): Predicting Prognosis after Neoadjuvant Chemotherapy (NAC) in Breast Cancer Patients.

OBJECTIVE: Axillary lymph node status is an important prognostic factor in breast cancer (BC). Residual nodal disease burden after neoadjuvant chemotherapy (NAC) is one of the important prognostic factors to determine the prognosis and in the treatment of BC. Lymph node ratio (LNR) defined as the ratio of the number of positive lymph nodes to total excised axillary lymph nodes, may be a stronger determinant of prognosis than pN in axillary nodal staging, although there is very limited data evaluating its prognostic value in the setting of NAC. In this cohort of patients, we studied the utility of LNR in predicting recurrence and overall survival (OS) after NAC. MATERIALS AND METHODS: An Institutional cancer registry was queried from 2009 to 2014 for women with axillary node-positive BC with no evidence of distant metastasis, and who received NAC followed by surgery for loco-regional treatment (axillary dissection with breast conserving surgery or total mastectomy). Patients with axillary complete response were excluded. Locoregional recurrence (LRR), distant recurrence (DR) and overall survival (OS) rates were reviewed regarding pN and LNR. RESULTS: A total of 179 patients were analyzed. Median follow up time was 24 [25%, 75%: 13-42] months. Patients with pN1 in comparison to pN2 and pN3 had lower rate of LRR (9% vs. 15% and 14%, respectively; p=0.41), lower rate of DR (14% vs. 25% and 27%, respectively, p=0.16) and increased rate of OS (89% vs. 79% and 78%, respectively, p=0.04). In comparison to patients with LNR >20%, patients with LNR ≤20% had lower LRR (9% vs. 14%, p=0.25), lower DR (13% vs. 27%, p=0.01) and improved OS (89% vs. 79%, p=0.02) rates. In the pN1 group, patients who had a LNR >20% had higher DR (22% vs. 14%, p=0.48) rates in comparison to patients with LNR ≤20%. In ER/PR (+) patients who had LNR ≤20% DR was 6% compared with 23% in patient who had LNR >20% (p=0.02), and in triple negative patients' OS rate was significantly better compared the LNR less/equal or more than 20% (71% vs 33%, p=0.001). CONCLUSION: Our study demonstrated that LNR adds valuable information for the prognosis after NAC and this additional information should be considered when deciding further treatment and follow-up for patients who had residual tumor burden on the axilla. This observation should be tested in a larger study.

Breast Cancer in Turkey; An Analysis of 20.000 Patients with Breast Cancer.

OBJECTIVE: Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths in women in Turkey. This study presents the characteristics of patients registered in National Breast Cancer Registry Program of Turkish Federation of Breast Diseases Societies. MATERIALS AND METHODS: The registry contains 242 variables under 10 categories and 699 questions. Patients were recorded (online and offline) from nationwide breast centers around Turkey. RESULTS: Twenty-thousand patients were registered between May 2005 and April 2017 at 36 centers. After data cleaning, 19,503 women were included in the study. The median age at diagnosis was 51 [14-97]; 17.2% were younger than 40 and 37.2% were premenopausal; 13.6% were nulliparous. Breast conserving surgery rate was 39.3%. Histopathology was invasive ductal cancer in 77%. Majority of patients had stage II cancer (48.3%). Estrogen, progesterone and HER-2 receptor positivity rates in invasive breast cancer were 72.5%, 62.5% and 21.8%, respectively. The mean tumor diameter was 2.5±1.7 cm. During the mean 51.6 months of follow-up, the local/regional and systemic recurrence rates were 3.7% and 5.2%, respectively; five and 10-year overall survival rates were 86% and 76%. CONCLUSION: Despite increasing number of screening centers and free-of-charge mammography (ages 40 to 69) and mobile screening systems in recent years, a significant portion of patients were diagnosed at advanced stage due to lack of breast cancer awareness. In contrast with the study published 5 years ago, there was a decrease in the rate of pre-menopausal women and an increase in the breast conserving surgery.