Feasibility of risk assessment for breast cancer molecular subtypes.

PURPOSE: Few breast cancer risk assessment models account for the risk profiles of different tumor subtypes. This study evaluated whether a subtype-specific approach improves discrimination. METHODS: Among 3389 women who had a screening mammogram and were later diagnosed with invasive breast cancer we performed multinomial logistic regression with tumor subtype as the outcome and known breast cancer risk factors as predictors. Tumor subtypes were defined by expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) based on immunohistochemistry. Discrimination was assessed with the area under the receiver operating curve (AUC). Absolute risk of each subtype was estimated by proportioning Gail absolute risk estimates by the predicted probabilities for each subtype. We then compared risk factor distributions for women in the highest deciles of risk for each subtype. RESULTS: There were 3,073 ER/PR+ HER2 - , 340 ER/PR +HER2 + , 126 ER/PR-ER2+, and 300 triple-negative breast cancers (TNBC). Discrimination differed by subtype; ER/PR-HER2+ (AUC: 0.64, 95% CI 0.59, 0.69) and TNBC (AUC: 0.64, 95% CI 0.61, 0.68) had better discrimination than ER/PR+HER2+ (AUC: 0.61, 95% CI 0.58, 0.64). Compared to other subtypes, patients at high absolute risk of TNBC were younger, mostly Black, had no family history of breast cancer, and higher BMI. Those at high absolute risk of HER2+ cancers were younger and had lower BMI. CONCLUSION: Our study provides proof of concept that stratifying risk prediction for breast cancer subtypes may enable identification of patients with unique profiles conferring increased risk for tumor subtypes.

Racial Disparities in Breast Cancer Genetic Testing May be Mitigated by Counseling.

BACKGROUND: Currently, racial disparities exist in access to genetic testing. Recent developments have helped narrow the gap in accessibility. The purpose of this study was to determine whether racial disparities in genetic consultation attendance and completion of genetic testing persist, and, if so, factors that contribute to under-utilization of these resources. METHODS: A single-institution retrospective review of breast patients referred for genetic counseling between 2017 and 2019 was performed. Univariate and multivariate logistic regression evaluated factors associated with genetic counseling attendance and genetic testing. RESULTS: A total of 596 patients were referred for genetic counseling: 433 (72.7%) white; 138 (23.2%) black; and 25 (4.2%) other or unknown. In multivariate analysis, black patients, patients without breast cancer family history, and patients without a current cancer diagnosis, classified as high risk, were significantly less likely to attend their genetics appointment (p = 0.010, p = 0.007, p = 0.005, respectively). Age, insurance type, distance from facility, and need for chemotherapy did not significantly impact consult completion rate. Of the patients who completed a genetic consult, 84.4% (n = 248) had genetic testing and 17.7% (n = 44) had a pathogenic variant. For patients who attended counseling, there were no significant factors that were predictive with receipt of genetic testing. CONCLUSIONS: In this study, there was a significant association between race and attending genetic counseling. Once counseled, most patients went on to receive genetic testing, and racial disparities in testing disappeared, emphasizing the value of providing additional education about the importance and purpose of genetic testing.

Penetrance of male breast cancer susceptibility genes: a systematic review.

PURPOSE: Several male breast cancer (MBC) susceptibility genes have been identified, but the MBC risk for individuals with a pathogenic variant in each of these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes to better summarize current estimates of penetrance. METHODS: A search query was developed to identify MBC-related papers indexed in PubMed/MEDLINE. A validated natural language processing method was applied to identify papers reporting penetrance estimates. These penetrance studies' bibliographies were reviewed to ensure comprehensiveness. We accessed the potential ascertainment bias for each enrolled study. RESULTS: Fifteen penetrance studies were identified from 12,182 abstracts, covering five purported MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2. Cohort (n = 6, 40%) and case-control (n = 5, 33%) studies were the two most common study designs, followed by family-based (n = 3, 20%), and a kin-cohort study (n = 1, 7%). Seven of the 15 studies (47%) adjusted for ascertainment adequately and therefore the MBC risks reported by these seven studies can be considered applicable to the general population. Based on these seven studies, we found pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 show an increased risk for MBC. The association between BRCA1 and MBC was not statistically significant. CONCLUSION: This work supports the conclusion that pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 increase the risk of MBC, whereas pathogenic variants in BRCA1 may not be associated with increased MBC risk.

Nipple-Sparing Mastectomy versus Skin-Sparing Mastectomy: Does Saving the Nipple Impact Short- and Long-Term Patient Satisfaction?

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe alternative to skin-sparing mastectomy (SSM). This study evaluated whether NSM patients were more satisfied than SSM patients in short- and long-term follow-up. METHODS: Women who underwent NSM or SSM between 2009 and 2019 completed a postoperative BREAST-Q survey at least 1 year after surgery and patient characteristics were compared. Patient satisfaction at 1-5 years and 6-10 years after NSM and SSM were analyzed. RESULTS: Overall, 431 patients were included; 247 had NSM and 184 had SSM 1-10 years prior to BREAST-Q survey completion. SSM patients were older, had higher body mass index (BMI), larger breast weight, and more hypertension than NSM patients, but oncologic treatments were similar between groups. BREAST-Q Psychosocial Well-Being and Sexual Well-Being scores were significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort; however, scores attenuated in the 6-10 years cohort. Satisfaction with breasts was nearly significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort (p = 0.056), but no different in the 6-10 years cohort. Receipt of adjuvant chemotherapy, receipt of postmastectomy radiation therapy, and BMI ≥30 were independent risk factors for dissatisfaction with breasts. CONCLUSIONS: Women who are not candidates for NSM should be reassured that long-term qualify of life is not significantly different between SSM and NSM. Dissatisfaction with reconstructed breasts is linked with other factors (besides the nipple), which patients should be made aware of at the time of surgical decision making.

Performance of a novel protease-activated fluorescent imaging system for intraoperative detection of residual breast cancer during breast conserving surgery.

PURPOSE: Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20-40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. METHODS: We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. RESULTS: Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81-5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. CONCLUSIONS: Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.

Management and outcomes of men diagnosed with primary breast cancer.

BACKGROUND: Fewer than 1% of all breast cancers occur in men. As a result, a distinct lack of data exists regarding the management and outcomes in this cohort. METHODS: Any male patient with pathologically confirmed breast cancer diagnosed between August 2000 and October 2017 at either Massachusetts General Hospital or Brigham and Women's Hospital/Dana-Farber Cancer Institute and their affiliate satellite locations were included. Primary chart review was used to assess clinical and pathologic characteristics. Patient and treatment variables were reported via descriptive statistics. Local-regional failure (LRF), overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method. RESULTS: 100 patients were included in this study. Median follow-up was 112 months (range 1-220 months). Approximately 1/3 of patients experienced at least a 3-month delay to presentation. 83 patients ultimately underwent mastectomy as definitive surgical treatment. 46 patients received adjuvant radiation therapy, and 37 patients received chemotherapy. Of 82 hormone receptor-positive patients with invasive cancer, 94% (n = 77) received endocrine therapy. Of the fifty-eight patients who underwent genetic testing, 15 (26%) tested positive. The 5-year OS, BCSS, DFS, and LRF rates were 91.5%, 96.2%, 86%, and 4.8%, respectively. Delay to presentation was not associated with worse survival. CONCLUSIONS: Male breast cancer remains a rare diagnosis. Despite this, the majority of patients in this study received standard of care therapy and experienced excellent oncologic outcomes. Penetration for genetic testing improved over time.

Non-medullary Thyroid Cancer Susceptibility Genes: Evidence and Disease Spectrum.

BACKGROUND: The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention. OBJECTIVE: The aim of this study was to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes. METHODS: Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity. RESULTS: Among 25 candidate genes, 10 (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions. CONCLUSION: Twelve genes predisposing to NMTC and their associated disease spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.

Breast imaging, breast surgery, and cancer genetics in the age of COVID-19.

BACKGROUND: The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID-19) on breast cancer screening, breast surgery, and genetics consultations. METHODS: User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the use of 3 breast cancer services, namely, breast imaging, breast surgery, and genetics consultation. Changes in the use of these services during the study period were analyzed. RESULTS: All 3 services experienced significant declines after the COVID-19 outbreak. The decline in breast surgery began during the week of March 8, followed by breast imaging and genetics consultation (both of which began during the week of March 15). Breast imaging experienced the most significant reduction, with an average weekly decline of 61.7% and a maximum decline of 94.6%. Breast surgery demonstrated an average weekly decline of 20.5%. When surgical consultation was stratified as breast cancer versus no breast cancer, the decrease among in non-breast cancer patients was more significant than that of patients with breast cancer (a decline of 66.8% vs 11.5% from the pre-COVID average weekly volume for non-breast cancer patients and patients with breast cancer, respectively). During the week of April 5, use of genetics consultations dropped to 39.9% of the average weekly volumes before COVID-19. CONCLUSIONS: COVID-19 has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment.

Node-Positive Patients Treated with Neoadjuvant Chemotherapy Can Be Spared Axillary Lymph Node Dissection with Wireless Non-Radioactive Localizers.

BACKGROUND: Targeted axillary dissection (TAD) involves sentinel lymph node biopsy (SLNB) and excision of a biopsy-proven node marked by a clip. This study evaluates the feasibility of non-radioactive wireless localizers for targeted excision of clipped axillary lymph nodes. METHODS: We identified biopsy-proven, node-positive breast cancer patients treated with neoadjuvant therapy (NAT) and TAD from 2016 to 2020, and included those with a clipped node localized using SAVI SCOUT, Magseed, or RFID Tag. Primary outcome measures were (1) successful localization (ultrasound or mammographic-guided placement < 10 mm from target), and (2) retrieval of the clipped node during TAD, documented by specimen radiography or gross visualization. Secondary outcomes included rates of completion axillary lymph node dissection (cALND) and complications. RESULTS: Overall, 57 patients were included; 1 (1.8%) patient had no clip visible at the time of localization, and no radiographic confirmation of clip placement at the time of biopsy, and was therefore excluded. In the remaining 56 patients, localization was successful in 53 (94.6%) patients and the clipped node was retrieved during TAD in 51 (91.1%) patients. Twenty-three of 27 (85.2%) ypN0 patients were spared cALND; 3 (11.1%) patients had cALND for failed clipped node retrieval during TAD, and 1 (3.7%) for false-positive frozen section. In patients with TAD alone, the rates of axillary seroma and infection were 20.0% and 8.6%, respectively. CONCLUSIONS: Wireless non-radioactive localizers are feasible for axillary localization after NAT, with high success rates of retrieving clipped nodes. The lack of signal decay is an advantage of these devices, allowing flexibility in timing of placement.

Legacy Genetic Testing Results for Cancer Susceptibility: How Common are Conflicting Classifications in a Large Variant Dataset from Multiple Practices?

PURPOSE: The classification of germline variants may differ between labs and change over time. We apply a variant harmonization tool, Ask2Me VarHarmonizer, to map variants to ClinVar and identify discordant variant classifications in a large multipractice variant dataset. METHODS: A total of 7496 variants sequenced between 1996 and 2019 were collected from 11 clinical practices. Variants were mapped to ClinVar, and lab-reported and ClinVar variant classifications were analyzed and compared. RESULTS: Of the 4798 unique variants identified, 3699 (77%) were mappable to ClinVar. Among mappable variants, variants of unknown significance (VUS) accounted for 74% of lab-reported classifications and 60% of ClinVar classifications. Lab-reported and ClinVar discordances were present in 783 unique variants (21.2% of all mappable variants); 121 variants (2.5% of all unique variants) had within-practice lab-reported discordances; and 56 variants (1.2% of all unique variants) had lab-reported discordances across practices. The unmappable variants were associated with a higher proportion of lab-reported pathogenic classifications (50% vs. 21%, p < 0.0001) and a lower proportion of lab-reported VUS classifications (46% vs. 74%, p < 0.0001). CONCLUSIONS: Our study shows that discordant variant classification occurs frequently, which may lead to inappropriate recommendations for prophylactic treatments or clinical management.

Novel Body Composition Predictors of Outcome in Patients With Angiosarcoma of the Breast: A Preliminary Study.

OBJECTIVE: The aim of the study was to determine abdominal and breast adipose tissue parameters on 18-fluorodeoxyglucose positron emission tomography/computed tomography (CT) that may serve as outcome predictors in breast angiosarcoma patients. MATERIALS: Women with breast angiosarcoma (n = 13) who underwent 18-fluorodeoxyglucose positron emission tomography/CT were identified. A control group was selected (n = 25). Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were assessed on unenhanced computed tomographies. Breast adipose tissue (BAT) volumes of the uninvolved breast were quantified. Metabolic activity of VAT, SAT, and BAT was calculated (standardized uptake value [SUV]). RESULTS: Breast angiosarcoma patients had higher metabolic activity of VAT compared with controls (SUV 0.93 ± 0.39 vs 0.64 ± 0.11, P = 0.044). Within the patient group, there were 6 deaths (46.2%). Patients who died had higher SAT activity (SUV 0.52 ± 0.24 vs 0.29 ± 0.06, P = 0.027) and higher BAT metabolic activity (SUV 0.48 ± 0.20 vs 0.27 ± 0.11, P = 0.045) compared with nondeceased patients. CONCLUSIONS: Patients with breast angiosarcoma have higher metabolic activity of VAT. Higher abdominal SAT and higher BAT metabolic activity of the uninvolved breast might predict mortality.

Natural language processing to facilitate breast cancer research and management.

The medical literature has been growing exponentially, and its size has become a barrier for physicians to locate and extract clinically useful information. As a promising solution, natural language processing (NLP), especially machine learning (ML)-based NLP is a technology that potentially provides a promising solution. ML-based NLP is based on training a computational algorithm with a large number of annotated examples to allow the computer to "learn" and "predict" the meaning of human language. Although NLP has been widely applied in industry and business, most physicians still are not aware of the huge potential of this technology in medicine, and the implementation of NLP in breast cancer research and management is fairly limited. With a real-world successful project of identifying penetrance papers for breast and other cancer susceptibility genes, this review illustrates how to train and evaluate an NLP-based medical abstract classifier, incorporate it into a semiautomatic meta-analysis procedure, and validate the effectiveness of this procedure. Other implementations of NLP technology in breast cancer research, such as parsing pathology reports and mining electronic healthcare records, are also discussed. We hope this review will help breast cancer physicians and researchers to recognize, understand, and apply this technology to meet their own clinical or research needs.

Atypical ductal hyperplasia in men with gynecomastia: what is their breast cancer risk?

PURPOSE: Atypical ductal hyperplasia (ADH) significantly increases the risk of breast cancer in women. However, little is known about the implications of ADH in men. METHODS: Review of 932 males with breast pathology was performed to identify cases of ADH. Patients were excluded if ADH was upgraded to cancer on excision, or if they had contralateral breast cancer. Cases were reviewed to determine whether any male with ADH developed breast cancer. RESULTS: Nineteen males were diagnosed with ADH from June 2003 to September 2018. All had gynecomastia. Surgical procedure was mastectomy in 8 patients and excision/reduction in 11. One patient had their nipple areola complex removed, and 1 required a free nipple graft. Median patient age at ADH diagnosis was 25 years (range 18-72 years). Of the 14 patients with bilateral gynecomastia, 10 had bilateral ADH and 4 had unilateral. Five cases of ADH were described as severe, bordering on ductal carcinoma in situ. No patient reported a family history of breast cancer. No patient took tamoxifen. At a mean follow-up of 75 months (range 4-185 months), no patient developed breast cancer. CONCLUSION: Our study is the first to provide follow-up information for males with ADH. With 6 years of mean follow-up, no male in our series has developed breast cancer. This suggests that either ADH in men does not pose the same risk as ADH in women or that surgical excision of symptomatic gynecomastia in men effectively reduces the risk of breast cancer.

Incidental breast carcinoma: incidence, management, and outcomes in 4804 bilateral reduction mammoplasties.

INTRODUCTION: Bilateral reduction mammoplasty is one of the most common plastic surgery procedures performed in the U.S. This study examines the incidence, management, and prognosis of incidental breast cancer identified in reduction specimens from a large cohort of reduction mammoplasty patients. METHODS: Breast pathology reports were retrospectively reviewed for evidence of incidental cancers in bilateral reduction mammoplasty specimens from five institutions between 1990 and 2017. RESULTS: A total of 4804 women met the inclusion criteria of this study; incidental cancer was identified in 45 breasts of 39 (0.8%) patients. Six patients (15%) had bilateral cancer. Overall, the maximum diagnosis by breast was 16 invasive cancers and 29 ductal carcinomas in situs. Thirty-three patients had unilateral cancer, 15 (45.5%) of which had high-risk lesions in the contralateral breast. Twenty-one patients underwent mastectomy (12 bilateral and nine unilateral), residual cancer was found in 10 in 25 (40%) therapeutic mastectomies. Seven patients did not undergo mastectomy received breast radiation. The median follow-up was 92 months. No local recurrences were observed in the patients undergoing mastectomy or radiation. Three of 11 (27%) patients who did not undergo mastectomy or radiation developed a local recurrence. The overall survival rate was 87.2% and disease-free survival was 82.1%. CONCLUSIONS: Patients undergoing reduction mammoplasty for macromastia have a small but definite risk of incidental breast cancer. The high rate of bilateral cancer, contralateral high-risk lesions, and residual disease at mastectomy mandates thorough pathologic evaluation and careful follow-up of these patients. Mastectomy or breast radiation is recommended for local control given the high likelihood of local recurrence without either.

Pathologic findings in reduction mammoplasty specimens: a surrogate for the population prevalence of breast cancer and high-risk lesions.

PURPOSE: Mammoplasty removes random samples of breast tissue from asymptomatic women providing a unique method for evaluating background prevalence of breast pathology in normal population. Our goal was to identify the rate of atypical breast lesions and cancers in women of various ages in the largest mammoplasty cohort reported to date. METHODS: We analyzed pathologic reports from patients undergoing bilateral mammoplasty, using natural language processing algorithm, verified by human review. Patients with a prior history of breast cancer or atypia were excluded. RESULTS: A total of 4775 patients were deemed eligible. Median age was 40 (range 13-86) and was higher in patients with any incidental finding compared to patients with normal reports (52 vs. 39 years, p = 0.0001). Pathological findings were detected in 7.06% (337) of procedures. Benign high-risk lesions were found in 299 patients (6.26%). Invasive carcinoma and ductal carcinoma in situ were detected in 15 (0.31%) and 23 (0.48%) patients, respectively. The rate of atypias and cancers increased with age. CONCLUSION: The overall rate of abnormal findings in asymptomatic patients undergoing mammoplasty was 7.06%, increasing with age. As these results are based on random sample of breast tissue, they likely underestimate the prevalence of abnormal findings in asymptomatic women.

Performance of Screening Breast MRI across Women with Different Elevated Breast Cancer Risk Indications.

Background Screening breast MRI is recommended for women with BRCA mutation or a history of chest radiation, but guidelines are equivocal for MRI screening of women with a personal history of breast cancer or high-risk lesion. Purpose To evaluate screening breast MRI performance across women with different elevated breast cancer risk indications. Materials and Methods All screening breast MRI examinations performed between 2011 and 2014 underwent retrospective medical record review. Indications for screening were as follows: BRCA mutation carrier or history of chest radiation (BRCA/RT group), family history of breast cancer (FH group), personal history of breast cancer (PH group), and history of high-risk lesion (HRL group). Screening performance metrics were calculated and compared among indications by using logistic regression adjusted for age, available prior MRI, mammographic density, examination year, and multiple risk factors. Results There were 5170 screening examinations in 2637 women (mean age, 52 years; range, 23-86 years); 67 breast cancers were detected. The cancer detection rate (CDR) was highest in the BRCA/RT group (26 per 1000 examinations; 95% confidence interval [CI]: 16, 43 per 1000 examinations), intermediate for those in the PH and HRL groups (12 per 1000 examinations [95% CI: 9, 17 per 1000 examinations] and 15 per 1000 examinations [95% CI: 7, 32 per 1000 examinations], respectively), and lowest for those in the FH group (8 per 1000 examinations; 95% CI: 4, 14 per 1000 examinations). No difference in CDR was evident for the PH or HRL group compared with the BRCA/RT group (P = .14 and .18, respectively). The CDR was lower for the FH group compared with the BRCA/RT group (P = .02). No difference was evident in positive predictive value for biopsies performed (PPV3) for the BRCA/RT group (41%; 95% CI: 26%, 56%) compared with the PH (41%; 95% CI: 31%, 52%; P = .63) or HRL (36%, 95% CI: 17%, 60%; P = .37) groups. PPV3 was lower for the FH group (14%; 95% CI: 8%, 25%; P = .048). Conclusion Screening breast MRI should be considered for women with a personal history of breast cancer or high-risk lesion. Worse screening MRI performance in patients with a family history of breast cancer suggests that better risk assessment strategies may benefit these women. © RSNA, 2019.

Trends in Unilateral and Contralateral Prophylactic Mastectomy Use in Ductal Carcinoma In Situ of the Breast: Patterns and Predictors.

BACKGROUND: Increased use of contralateral prophylactic mastectomy (CPM) as treatment for ductal carcinoma in situ (DCIS) in the US was first noted in the early 2000s. Optimization of treatment guidelines for DCIS requires an understanding of current surgical treatment trends, particularly as they may differ by patient sociodemographic and community resource factors. OBJECTIVE: The aim of this study was to evaluate surgical treatment trends among US women with DCIS and to assess the impact of sociodemographic and community resource factors on surgical treatment choice. METHODS: The Surveillance, Epidemiology, and End Results dataset was queried for women aged 40 years and older who were diagnosed with unilateral DCIS between 2000 and 2014. Annual mastectomy rates were compared over time by age and race/ethnicity. Multivariable logistic regressions were performed to identify predictors of mastectomy use, with patient sociodemographics, tumor characteristics, and community resource factors (i.e. plastic surgeon density) as covariates. RESULTS: A total of 130,731 women with DCIS met the inclusion criteria. Overall mastectomy rates remained relatively unchanged over the study period (25-30%). CPM use increased for all age and race/ethnic groups, with the greatest increase exhibited by women aged 40-49 years [relative to 2000; 2014 odds ratio (OR) 10.6]. With respect to community resource factors, CPM use, as opposed to unilateral mastectomy, was associated with counties of higher education level (OR 1.52), higher income level (OR 1.22), and lower plastic surgeon density (OR 1.26). CONCLUSION AND RELEVANCE: While the popularity of mastectomy in the management of DCIS has remained relatively unchanged since the turn of the century, the use of CPM has risen substantially. Younger women with DCIS have seen the greatest increase in CPM use, a choice that remains influenced by race/ethnicity as well as income, education, and health resource availability. Until clinical risk stratifiers of DCIS are identified, the surgical decision-making paradigm must be improved so that treatment choice remains sensitive to cultural differences but becomes independent of income, education, and health resource availability.

Evaluating the Rate of Upgrade to Invasive Breast Cancer and/or Ductal Carcinoma In Situ Following a Core Biopsy Diagnosis of Non-classic Lobular Carcinoma In Situ.

BACKGROUND: A diagnosis of non-classic lobular carcinoma in situ (NC-LCIS) encompasses a variety of lesions with poorly characterized natural history. We evaluated upgrade rates and factors associated with upgrade to malignancy following a core biopsy diagnosis of NC-LCIS, and its natural history. METHODS: Upon Institutional Review Board approval, pathology databases were searched for NC-LCIS core biopsy diagnoses (carcinoma in situ [CIS], CIS with ductal and lobular features [CIS/DLF], pleomorphic LCIS [P-LCIS], variant LCIS [V-LCIS], LCIS with necrosis). Cases with available core and excision pathology were included, while cases with concurrent ipsilateral invasive carcinoma (IC), ductal carcinoma in situ (DCIS), and/or atypical ductal hyperplasia were excluded. RESULTS: Overall, 121 NC-LCIS cases were identified from 1998 to 2017. We excluded 46 cases with concurrent cancer; 75 patients with 76 NC-LCIS core biopsy diagnoses followed by excision formed our study cohort. Median age was 56 years (range 41-83), and all imaging findings were classified as Breast Imaging Reporting and Data System 4; calcifications were the most common biopsy indication (80%). Excision yielded malignancy in 27 (36%) patients (IC 17, 63%; DCIS alone 10, 37%). We were unable to identify radiologic or pathologic features predictive of upgrade. Of 49 pure NC-LCIS cases, 15 (31%) had mastectomy, 9 (18%) had excision and radiation, and 25 (51%) had excision alone. At a median follow-up of 58 months (range 1-224), 1/25 (4%) patients with excision alone developed ipsilateral DCIS 14 months later. CONCLUSIONS: In this series of NC-LCIS, 36% of cases were upgraded, supporting routine excision. We were unable to identify predictors of upgrade. Among 25 patients with pure NC-LCIS, only one patient developed a future ipsilateral cancer. Further study of the natural history of NC-LCIS is warranted.