HER-2 low status in early-stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series.

PURPOSE: HER2 overexpression has a central role in breast cancer carcinogenesis and is associated with poor prognosis if untreated. Lately, identification of HER2-low breast cancer has been proposed to select patients for novel HER2-directed chemotherapy and includes cancers with immunohistochemistry 1 + or 2 + with negative FISH, encompassing approximately 55-60% of all breast carcinomas. In early-stage breast cancer, the prognostic significance of HER2 low-disease is less well understood, with a particular paucity of data evaluating the prevalence and implications of HER2-low status in invasive lobular carcinoma (ILC). METHODS: We evaluated 666 stage I-III ILC tumors from a prospectively maintained institutional database, comparing clinicopathologic features and disease-free survival (DFS) using a multivariable Cox proportional hazards model. RESULTS: HER2-low status was common in this cohort of patients with ILC, but most clinicopathologic features did not differ between HER2-low and HER2-negative cases. However, when adjusting for tumor size, number of positive nodes, ER/PR status, and local therapy received, patients with HER2-low status had worse disease-free survival (DFS) than those with HER2-negative tumors (hazard ratio 2.0, 95% confidence interval 1.0-4.1, p = 0.05). CONCLUSION: This difference in DFS supports the notion that HER2-low and HER2-negative early stage ILC may differ clinically, despite similar clinicopathologic features. Further investigation into the potential benefit of HER2 targeted therapy in HER2-low early-stage breast cancer, and specifically lobular cancer, is warranted to ensure optimal outcomes in this distinct tumor subtype.

Quantifying hormone receptor status in lobular breast cancer in an institutional series: the relationship between estrogen and progesterone receptor status and outcomes.

PURPOSE: Recent guidelines defined a new reporting category of ER-low-positive breast cancer based on immunohistochemistry (IHC). While low positivity of either hormone receptor is uncommon in invasive lobular carcinoma (ILC), we sought to investigate whether relatively low hormone receptor positivity was associated with tumor characteristics and patient outcomes in a single institutional cohort. METHODS: We searched an institutional database for cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, ER was classified as low, medium, or high as defined by ER staining of 10-69%, 70-89%, and ≥ 90% respectively. PR low and high tumors were defined by < 20%, or ≥ 20% staining respectively. We used chi-squared tests, t-tests, and Cox proportional hazards models to evaluate associations between ER/PR categories and tumor characteristics or disease-free survival (DFS). RESULTS: The cohort consisted of 707 ILC cases, with 11% of cases categorized as ER low, 15.1% as medium, and 73.8% as high. The majority (67.6%) were PR high. Patients with ER low/medium expression were significantly younger, and more likely to also have PR low and/or HER2 positive tumors compared to those that were ER high. In a Cox proportional hazards model adjusting for age, stage, grade, pleomorphic histology, and treatment, ER category was not prognostic for DFS, but PR negative and PR low status each had significantly worse DFS compared to PR high status (HR 3.5, 95% CI 1.8-6.7, p < 0.001; and HR 2.0, 95% CI 1.1-3.5, p = 0.015, respectively). CONCLUSION: These findings highlight the relevance of quantifying ER and PR within ILC.

Nipple-Sparing Mastectomies in Patients over the Age of 60 Years: Factors Associated with Surgical Outcomes.

BACKGROUND: Nipple-sparing mastectomy (NSM) outcomes in the elderly have not been well characterized. The goal of this study was to evaluate NSM outcomes in patients over age 60. PATIENTS AND METHODS: A single-institution retrospective cohort study was performed for NSM patients over the age of 60 from January 2004 to January 2022. Demographic, intraoperative, and postoperative variables were collected. RESULTS: We identified 136 women who underwent a total of 200 NSMs at a mean age 65.2 years and with mean body mass index of 25. Most (56%) had invasive breast cancer, requiring neoadjuvant chemotherapy in 15%, and 17.5% had radiation prior to NSM. A total of 91% had immediate tissue expander placement. The infection rate was 19%, with 11.5% requiring expander explantation in the follow-up period. In binomial logistic regression analysis, prior radiation increased the odds of any complication by 2.9 (OR 2.93, CI 1.30-6.58, p = 0.009) and increased the odds of infection by 5.7 (OR 5.70, CI 1.95-16.66, p = 0.001), but no associations were seen for other covariates including age, comorbidities, prior chemotherapy, or presence of invasive disease. Diabetes increased the odds of wound breakdown specifically by 9.0 (OR 8.97, CI 2.01-39.92, p = 0.004). Local recurrence was 3% in mean 3.4-year follow-up. CONCLUSIONS: Our data support NSM in patients over the age of 60 years with acceptable outcomes within the standard of care. Locoregional recurrence was within the cited range of 0-5%, and only diabetes and prior radiation were associated with reconstructive complications. NSM should thus be offered when appropriate regardless of increased age to achieve oncologic and reconstructive goals.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Immediate Versus Delayed-Immediate Autologous Breast Reconstruction After Nipple-Sparing Mastectomy.

INTRODUCTION: Autologous reconstruction following nipple-sparing mastectomy (NSM) is either performed in a delayed-immediate fashion, with a tissue expander placed initially at the time of mastectomy and autologous reconstruction performed later, or immediately at the time of NSM. It has not been determined which method of reconstruction leads to more favorable patient outcomes and lower complication rates. METHODS: We performed a retrospective chart review of all patients who underwent autologous abdomen-based free flap breast reconstruction after NSM between January 2004 and September 2021. Patients were stratified into 2 groups by timing of reconstruction (immediate and delayed-immediate). All surgical complications were analyzed. RESULTS: One hundred one patients (151 breasts) underwent NSM followed by autologous abdomen-based free flap breast reconstruction during the defined time period. Fifty-nine patients (89 breasts) underwent immediate reconstruction, whereas 42 patients (62 breasts) underwent delayed-immediate reconstruction. Considering only the autologous stage of reconstruction in both groups, the immediate reconstruction group experienced significantly more delayed wound healing, wounds requiring reoperation, mastectomy skin flap necrosis, and nipple-areolar complex necrosis. Analysis of cumulative complications from all reconstructive surgeries revealed that the immediate reconstruction group still experienced significantly greater cumulative rates of mastectomy skin flap necrosis. However, the delayed-immediate reconstruction group experienced significantly greater cumulative rates of readmission, any infection, infection requiring PO antibiotics, and infection requiring IV antibiotics. CONCLUSIONS: Immediate autologous breast reconstruction after NSM alleviates many issues seen with tissue expanders and delayed autologous reconstruction. Although mastectomy skin flap necrosis occurs at a significantly greater rate after immediate autologous reconstruction, it can often be managed conservatively.

Evaluation of Microvascular Autologous Breast Reconstruction in Patients Older Than 60 Years.

BACKGROUND: While free-flap breast reconstruction becomes more common, it is still approached with caution in older patients. Outcomes in the elderly population have not been well characterized, especially with regard to donor-site sequalae. This study compares microvascular autologous breast reconstruction outcomes in patients older and younger 60 years. METHODS: A single-institution retrospective review was performed for microvascular autologous breast reconstruction from January 2004 through January 2021. Demographic, intraoperative, and postoperative variables, including breast flap and donor-site complications, were evaluated. RESULTS: Five hundred forty-five breast free flaps were identified, of which 478 (87.8%) were performed on patients younger than 60 years (mean, 46.2 years) and 67 (12.2%) older than 60 years (mean, 64.8 years; P = 0.000). Hyperlipidemia was significantly higher in older patients (19.4% vs 9.6%, P = 0.016). Mean operative time was 46.3 minutes faster in the older cohort ( P = 0.030). There were no significant differences in free-flap loss, venous congestion, takeback, hematoma, seroma, wound healing, or infection. Interestingly, there were significantly more total breast flap complications (28.5% vs 16.4%, P = 0.038) and higher rates of fat necrosis (9.6% vs 1.5%, P = 0.026) in the younger cohort. Significantly more abdominal donor-site complications (43.3% vs 21.3%, P = 0.000) were seen in the older people, with increased wound breakdown ( P = 0.000) and any return to the operating room (20.9% vs 9.8%, P = 0.007). Older patients were also significantly more likely to require surgical correction of an abdominal bulge or hernia (10.4% vs 4%, P = 0.020). The mean follow-up was 1.8 years. CONCLUSIONS: Our data showed no worsening of individual breast flap outcomes in the older people. However, there were significantly more abdominal complications including surgical correction of abdominal bulge and hernia. This may be related to the inherent qualities of tissue aging and should be taken into consideration for flap selection. These results support autologous breast reconstruction in patients older than 60 years, but patients should be counseled regarding potentially increased abdominal donor-site sequelae.

Obesity and menopausal status impact the features and molecular phenotype of invasive lobular breast cancer.

PURPOSE: We investigated the relationship between obesity, menopausal status, and invasive lobular carcinoma (ILC), the second most common histological subtype of breast cancer. Specifically, we evaluated the association between body mass index (BMI), metabolic syndrome, the 21-gene Oncotype Recurrence Score (Oncotype RS), and pathological features in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2-negative ILC. METHODS: The study cohort included 491 patients from a prospectively maintained institutional database consisting of patients with stage I-III, HR-positive ILC who underwent surgical treatment between 1996 and 2019. RESULTS: Contrary to our expectations, we found that lower BMI was significantly associated with having higher Oncotype RS (18.9% versus 4.8%, p = 0.028) in post-menopausal patients, but was not related to tumor characteristics in pre-menopausal patients. Multivariate network analyses suggested a strong relationship between post-menopausal status itself and tumor characteristics, with lesser influence of BMI. CONCLUSION: These findings provide further insight into the recently appreciated heterogeneity within ILC and support the need for further investigation into the drivers of this disease and tailored treatment strategies.

High-level compliance to opt-out HIV testing in the emergency department (ED) of a large teaching hospital using the biochemistry sample as the sample type for HIV screening.

INTRODUCTION: HIV remains a key public health issue. National Institute for Health and Care Excellence and British HIV Association guidance recommends that patients should be offered HIV testing when admitted to hospital or attending emergency departments (EDs) in areas with a prevalence ≥ 2 per 1000. We report a novel method of testing and the first 3-year results from our HIV ED testing programme utilizing biochemistry samples for HIV testing, with the aim of improving uptake while ensuring no changes to clinical practice in EDs. METHODS: Routine ED HIV testing was implemented on 1 October 2018; it was initially opt-in and was subsequently changed to opt-out on 1 February 2019. HIV testing was added to all ED blood test order sets and was performed on the biochemistry samples of those aged 18-59 years. The age range was extended to include those aged 16+ years on 1 March 2021 along with a move to notional consent. RESULTS: A total of 78 333 HIV tests were performed from an estimated 110 683 attendees who had bloods taken in the same age range, demonstrating an overall 69.5% testing coverage. On implementation of opt-out testing after the first 4 months, the proportion of tests increased (from 57.9% to 69%). After increase in age range to 16+ years and a move to notional consent, the overall testing coverage improved to 74.2%. Of 1054 reactive results, 728 (69%) were known people living with HIV, eight (0.8%) were not contactable, two (0.2%) re-tested elsewhere and three (0.3%) declined a re-test. A total of 259 false-positives were determined by follow-up testing and 50 (4.8%) were newly diagnosed with HIV. An HIV diagnosis was suspected in only 22%, and 48% had never previously tested for HIV. CONCLUSIONS: An opt-out HIV testing programme with notional consent and using biochemistry samples within the ED is feasible, acceptable and provides an excellent opportunity to diagnose patients who do not perceive themselves to be at risk or have never tested before.

Risk of forced marriage amongst people with learning disabilities in the UK: Perspectives of South Asian carers.

BACKGROUND: People with intellectual disabilities are at increased risk of forced marriage compared to those without intellectual disabilities. In the UK, this risk is particularly, though not exclusively, associated with South Asian communities and is linked to the desire to secure long-term care. METHOD: Focus groups and semi-structured interviews were undertaken with South Asian parents and family carers (n = 22) of adults with intellectual disability and the resultant data thematically analysed. RESULTS: Although securing care for their intellectually disabled relative was identified as a key motivator for forced marriage, other important themes also emerged. These included cultural and religious beliefs about disability and marriage, and limited understanding of relevant laws. Factors militating against forced marriage were also identified, including fears of abuse and neglect. CONCLUSIONS: Implications for the provision of services and the need for improved access to information on forced marriage of people with intellectual disabilities are highlighted.

Genetic testing for neurodegenerative diseases: Ethical and health communication challenges.

Advances in genomic science are informing an expansion of genetic testing for neurodegenerative diseases, which can be used for diagnostic and predictive purposes and performed in both medical and consumer genomics settings. Such testing-which is often for severe and incurable conditions like Huntington's, Alzheimer's, and Parkinson's diseases-raises important ethical and health communication challenges. This review addresses such challenges in the contexts of clinical, research, and direct-to-consumer genetic testing; these include informed consent, risk estimation and communication, potential benefits and psychosocial harms of genetic information (e.g., genetic discrimination), access to services, education and workforce needs, and health policies. The review also highlights future areas of likely growth in the field, including polygenic risk scores, use of genetic testing in clinical trials, and return of individual research results.