Tumors, Treatments, and Trust: Cancer Characteristics, Outcomes, and Screening Uptake in Transgender and Gender-Diverse Patients.

BACKGROUND: More than 2.5 million adults in the United States identify as transgender or gender-diverse (TGD), but little data exist on cancer screening and care for this population. We examined cancer characteristics, screening adherence, genetic testing, and provider inclusive language for TGD patients with cancer. METHODS: This single institution retrospective cohort study identified TGD patients with cancer between 2000 and 2022. Demographic, clinicopathological, treatment, and screening data were collected, as well as data on gender-affirming care (GAC) and use of patients' personal pronouns in medical records. Descriptive statistics and regression analyses were used to report outcomes. RESULTS: Sixty unique patients with 69 cancer diagnoses were included: 63.3% were transgender women, 21.7% transgender men, 6.7% nonbinary, and 8.3% were genderqueer. Sixty-five percent had a family history of cancer. Only 46.2% of those who met genetic testing criteria were referred. On review of recommended cancer screening, colorectal screening had the greatest uptake (62%), followed by breast (48.3%), lung (35.7%), cervical (33.3%), and prostate (32%); 8.5% of cancers were diagnosed on screening. Individuals with Medicare had reduced odds of screening uptake (OR 0.07, 95% CI 0.01-0.58) versus private insurance. With respect to GAC, 73.3% used gender-affirming hormone therapy and 41% had gender-affirming surgery. After initiating GAC and asserting personal pronouns, 75% were referred to by incorrect name/pronouns in provider documentation. CONCLUSIONS: Our TGD cancer patient cohort had low rates of disease-specific cancer screening and inadequate genetic referrals. Many providers did not use appropriate patient names/pronouns. Provider and patient interventions are needed to ensure inclusive preventative and oncologic care for this marginalized population.

The Impact of a Breast Cancer Risk Assessment on the Decision for Gender-Affirming Chest Masculinization Surgery in Transgender and Gender-Diverse Individuals: A Pilot Single-Arm Educational Intervention Trial.

BACKGROUND: Persons assigned female or intersex at birth and identify as transgender and/or gender-diverse (TGD) may undergo gender-affirming chest masculinization surgery (GACMS); however, GACMS is not considered equivalent to risk-reducing mastectomies (RRM). This study aimed to estimate the prevalence of elevated breast cancer (BC) risk in TGD persons, compare self-perceived versus calculated risk, and determine how risk impacts the decision for GACMS versus RRM. METHODS: A prospective single-arm pilot educational intervention trial was conducted in individuals assigned female or intersex at birth, age ≥ 18 years, considering GACMS, without a BC history or a known pathogenic variant. BC risk was calculated using the Tyrer-Cuzik (all) and Gail models (age ≥ 35 years). Elevated risk was defined as ≥ 17%. RESULTS: Twenty-five (N = 25) participants were enrolled with a median age of 24.0 years (interquartile range, IQR 20.0-30.0 years). All were assigned female sex at birth, most (84%) were Non-Hispanic (NH)-White, 48% identified as transgender and 40% as nonbinary, and 52% had a first- and/or second-degree family member with BC. Thirteen (52%) had elevated risk (prevalence 95% confidence interval (CI) 31.3-72.2%). Median self-perceived risk was 12% versus 17.5% calculated risk (p = 0.60). Of the 13 with elevated risk, 5 (38.5%) underwent/are scheduled to undergo GACMS, 3 (23%) of whom underwent/are undergoing RRM. CONCLUSIONS: Over half of the cohort had elevated risk, and most of those who moved forward with surgery chose to undergo RRM. A BC risk assessment should be performed for TGD persons considering GACMS. Future work is needed to examine BC incidence and collect patient-reported outcomes. Trial Registration Number ClinicalTrials.gov (No. NCT06239766).

An Annual Symposium on Disparities in Milwaukee, WI, with a 2023 Focus on Older Adults with Cancer.

PURPOSE OF REVIEW: Cancer-related inequities are prevalent in Wisconsin, with lower survival rates for breast, colorectal, and lung cancer patients from marginalized communities. This manuscript describes the ongoing efforts at the Medical College of Wisconsin and potential pathways of community engagement to promote education and awareness in reducing inequities in cancer care. RECENT FINDINGS: While some cancer inequities are related to aggressive disease biology, health-related social risks may be addressed through community-academic partnerships via an open dialogue between the community members and academic faculty. To develop potential pathways of community-academic partnerships, an annual Cancer Disparities Symposium concept evolved as a pragmatic and sustainable model in an interactive learning environment. In this manuscript, we describe the programmatic development and execution of the annual Cancer Disparities Symposium, followed by highlights from this year's meeting focused on geriatric oncology as discussed by the speakers.

Divergent Cellular Expression Patterns of PD-L1 and PD-L2 Proteins in Breast Cancer.

PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression patterns of PD-L1 and PD-L2. PD-L1-positivity was higher in immune cells than in cancer cells (median = 5.0% vs. 0.0%; p = 0.001), whereas PD-L2-positivity was higher in cancer cells than immune cells (median = 30% vs. 5.0%; p = 0.001). Percent positivity of PD-L1 and PD-L2 were not correlated, neither in cancer cells nor immune cells. Based on a cut-point of ≥1% positivity, ER+ tumors (n = 23) were frequently PD-L2-positive (73.9%), whereas only 40.9% were PD-L1-positive. These data suggest differential control of cellular PD-L1 and PD-L2 expression in BC and a potential role for PD-L2 IHC as a complementary marker to PD-L1 to improve selection of aggressive ER+ BC that may benefit from anti-PD-1 therapy.

Risk Factors for Skin Flap and Nipple-Areolar Necrosis in Patients Undergoing Nipple-Sparing Mastectomy With Deep Inferior Epigastric Perforator Flap Reconstruction.

INTRODUCTION: Nipple-sparing mastectomy (NSM) with deep inferior epigastric perforator (DIEP) flap reconstruction is a surgical option for select patients with or at risk of breast cancer. However, post-operative skin flap and nipple-areolar complex (NAC) necrosis remain common complications. This study aimed to identify factors associated with necrosis in patients undergoing NSM with DIEP reconstruction. METHODS: A retrospective cohort study was performed from 2015 to 2023. 74 variables were analyzed in patients undergoing NSM with DIEP. Patients were stratified into 3 groups based on post-operative skin/NAC necrosis: none, partial thickness, and full thickness. Comparative and descriptive statistics were performed via t-tests, ANOVA, and chi-squared tests. RESULTS: 34 women with 31 breast cancers met inclusion. 44% experienced necrosis: 15% partial thickness and 29% full thickness. The majority were white (85.3%) with mean age of 50 years (SD = 9.11). In patients with immediate DIEP reconstruction, hypoperfused areas identified by SPY angiography increased risk of necrosis (P = .012). Approximately 50% of both partial thickness and full thickness necrosis patients had concerns on SPY angiography. Former smokers in the full thickness necrosis group had more pack years than those without necrosis (9 vs .65 pack years, P = .035). CONCLUSION: In patients receiving NSM with DIEP flap reconstruction, those with hypoperfusion on SPY angiography and longer smoking history had higher necrosis rates. This supports the continued used of SPY angiography and the role of pre-operative counseling in former smokers with increased pack years on their risk of necrosis and the role of preventative measures in the perioperative setting.

Does Neoadjuvant Chemotherapy in Clinical T1-T2 N0 Triple-Negative Breast Cancer Increase the Extent of Axillary Surgery?

BACKGROUND: Current management strategies for early-stage triple-negative breast cancer (TNBC) include upfront surgery to determine pathologic stage to guide chemotherapy recommendations, or neoadjuvant chemotherapy (NAC) to de-escalate surgery, elucidate tumor response, and determine the role of adjuvant chemotherapy. However, patients who receive NAC with residual pathological nodal (pN) involvement require axillary lymph node dissection (ALND) as they are Z11/AMAROS ineligible. We aimed to evaluate the impact of NAC compared with upfront surgery on pN status and ALND rates in cT1-2N0 TNBC. METHODS: The National Cancer Database (NCDB) was queried for women with operable cT1-2N0 TNBC from 2014 to 2019. Demographic, clinicopathologic, and treatment data were collected. Multivariable linear regression analysis was performed to assess the odds of pN+ disease and undergoing ALND. RESULTS: Overall, 55,624 women were included: 26.9% (n = 14,942) underwent NAC and 73.1% (n = 40,682) underwent upfront surgery. The NAC cohort was younger (mean age 52.9 vs. 61.3 years; p < 0.001) with more cT2 tumors (71.6% vs. 31.0%; p < 0.001), and had lower ALND rates (4.3% vs. 5.5%; p < 0.001). The upfront surgery cohort was more likely to have one to three pathologically positive nodes (12.1% vs. 6.5%; odds ratio [OR] 2.37, 95% confidence interval (CI) 2.17-2.58; p < 0.001) but there was no difference in the likelihood of ALND (OR 1.1, 95% CI 0.99-1.24; p = 0.08). CONCLUSION: Patients who underwent upfront surgery were more likely to be pN+; however, ALND rates were similar between the two cohorts. Thus, the use of NAC does not result in a higher odds of ALND and the decision for NAC should be individualized and based on modern guidelines and systemic therapy benefits.

Applications of Viscoelastic Testing in Breast Cancer Patients: A Systematic Review Focusing on Hypercoagulability and Free Flap Thrombosis.

Viscoelastic testing is a clinically available method to assess hypercoagulability. This systematic review aims to provide a comprehensive overview of the existing literature and the potential use of such testing in patients with breast cancer. A systematic literature search for studies investigating the application of viscoelastic testing for patients with breast cancer was conducted. Studies were included as long as they were original, peer-reviewed, and in the English language. Studies were excluded if they were review articles, did not include breast cancer patients, or if the full text was unavailable. This review identified 10 articles that met the inclusion criteria. Two of the studies utilized rotational thromboelastometry, and an additional four studies used thromboelastography, to assess hypercoagulability in patients with breast cancer. Three of the identified articles discussed the use of thromboelastometry in free flap breast reconstruction for patients with breast cancer. One study was a retrospective chart review looking at thromboelastography and microsurgical breast reconstruction. Current literature regarding the application of viscoelastic testing in breast cancer and free flap breast reconstruction is limited, with no randomized trials thus far. However, some studies suggest that there may be potential utility in viscoelastic testing to assess risk for thromboembolism in breast cancer patients, and future research in this area is warranted.

National trends in neoadjuvant chemotherapy utilization in patients with early-stage node-negative triple-negative breast cancer: the impact of the CREATE-X trial.

PURPOSE: Neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) allows for assessment of tumor pathological response and has survival implications. In 2017, the CREATE-X trial demonstrated survival benefit with adjuvant capecitabine in patients TNBC and residual disease after NAC. We aimed to assess national rates of NAC for cT1-2N0M0 TNBC before and after CREATE-X and examine factors associated with receiving NAC vs adjuvant chemotherapy (AC). METHODS: A retrospective cohort study of women with cT1-2N0M0 TNBC diagnosed from 2014 to 2019 in the National Cancer Database (NCDB) was performed. Variables were analyzed via ANOVA, Chi-squared, Fisher Exact tests, and a multivariate linear regression model was created. RESULTS: 55,633 women were included: 26.9% received NAC, 52.4% AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71 years, p < 0.01). NAC utilization significantly increased over time: 19.5% in 2014-15 (n = 3,465 of 17,777), 27.1% in 2016-17 (n = 5,140 of 18,985), and 33.6% in 2018-19 (n = 6,337 of 18,871, p < 0.001). On multivariate analysis, increased NAC was associated with younger age (< 50), non-Hispanic white race/ethnicity, lack of comorbidities, cT2 tumors, care at an academic or integrated-network cancer program, and diagnosis post-2017 (p < 0.05 for all). Patients with government-provided insurance were less likely to receive NAC (p < 0.01). Women who traveled > 60 miles for treatment were more likely to receive NAC (p < 0.01). CONCLUSION: From 2014 to 2019, NAC utilization increased for patients with cT1-2N0M0 TNBC. Racial, socioeconomic, and access disparities were observed in who received NAC vs AC and warrants interventions to ensure equitable care.

Systematic Review on Gender-Affirming Testosterone Therapy and the Risk of Breast Cancer: A Challenge for Physicians Treating Patients from Transgender and Gender-Diverse Populations.

Conflicting evidence exists about the risk of breast cancer in transgender and gender-diverse (TGD) patients treated with testosterone. This review aimed to summarize current knowledge regarding the risk of breast cancer associated with gender-affirming testosterone treatment (GATT). A systematic literature search using the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist was conducted in January 2023 through Ovid, Scopus, and Web of Science databases. English-language, peer-reviewed articles evaluating breast cancer in TGD patients after GATT that met the inclusion criteria were included. This review included 22 articles, with 14 case reports, 4 case series, and 4 retrospective cohort studies. The review identified 26 TGD patients who developed breast cancer post-GATT therapy, with inconclusive evidence on the relationship between testosterone and the risk of breast cancer in TGD patients. This uncertainty in part arises from the mechanisms governing testosterone's effects within breast tissue, with contrasting theories proposing both proliferative and antiproliferative impacts. Considering this ambiguity, it is imperative for healthcare providers to engage in informed discussions with patients prior to initiating hormone therapy to discuss potential adverse effects, including the possibility of breast cancer development in TGD individuals. Patient education and shared decision-making are essential components of responsible care in this context.

Frequent upregulation of HER2 protein in hormone-receptor-positive HER2-negative breast cancer after short-term neoadjuvant endocrine therapy.

BACKGROUND: Endocrine resistant metastatic disease develops in ~ 20-25% of hormone-receptor-positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors. METHODS: This was a single arm, interventional phase II clinical trial evaluating 4 weeks (± 1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥ 1 in IHC score following NET. RESULTS: Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p = 0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis. CONCLUSION: Short-term NET frequently and preferentially upregulates HER2 over other HER family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway. CLINICAL TRIAL REGISTRY: Trial registration number: NCT03219476.

National Trends in "Going Flat" After Mastectomy.

INTRODUCTION: The "Going Flat" movement became widely publicized in 2016 and provides information and support to women who choose to forego post-mastectomy breast reconstruction (PMBR). The objectives of this study were to evaluate temporal trends in PMBR to ascertain the potential impact of this movement and assess which factors are associated with going flat. METHODS: A retrospective cohort analysis was performed using the NCDB of women with non-metastatic breast cancer who underwent mastectomy between 2004 and 2019. Trends in going flat after mastectomy were examined and stratified by age (< 50, 50-69, ≥ 70). A multivariate logistic regression model was used to identify factors associated with going flat. RESULTS: 650,983 patients met the inclusion criteria: 244,201 (37.5%) underwent PMBR and 406,782 (62.5%) went flat. Among women < 70, rates of going flat steadily decreased from 2004 to 2015 and then stabilized after 2015, coinciding with the rise of the "Going Flat" movement. In multivariate analysis, non-White race, older age, increasing comorbidities, government provided insurance, treatment at a community program, radiotherapy, and adjuvant chemotherapy were associated with a higher likelihood of going flat (p < 0.001). CONCLUSION: In the first 2 years after the "Going Flat" movement, the number of women going flat after mastectomy has stabilized in women < 70 for the first time in over a decade. These trends suggest that the social and cultural impact of this movement may have contributed to the stabilization of PMBR rates.

Associations Between Hospital Volume and Overall Survival After Surgery in Older Patients with Breast Cancer.

BACKGROUND: High-volume hospitals (HVHs) are associated with improved overall survival (OS) following surgery for breast cancer compared with low-volume hospitals (LVHs). We examined this association in patients age ≥ 80 years and described patient and treatment characteristics associated with HVHs. PATIENTS AND METHODS: The National Cancer Database was queried for women age ≥ 80 years who underwent surgery for stage I-III breast cancer between 2005 and 2014. Hospital volume was defined as the average number of cases during the year of the patient's index operation and the year prior. Hospitals were categorized into HVHs and LVHs using penalized cubic spline analysis of OS. A cutoff of ≥ 270 cases/year defined HVHs. RESULTS: Among 59,043 patients, 9110 (15%) were treated at HVHs and 49,933 (85%) at LVHs. HVHs were associated with more non-Hispanic Black and Hispanic patients, earlier stage disease (stage I 54.9% vs. 52.6%, p < 0.001), higher rates of breast-conserving surgery (BCS) (68.3% vs. 61.4%, p < 0.001), and adjuvant radiation (37.5% vs. 36.1%, p = 0.004). Improved OS was associated with surgery at a HVH (HR 0.85, CI 0.81-0.88), along with receipt of adjuvant chemotherapy (HR 0.73, CI 0.69-0.77), endocrine therapy (HR 0.70, CI 0.68-0.72), and radiation (HR 0.66, CI 0.64-0.68). CONCLUSIONS: Among patients with breast cancer age ≥ 80 years, undergoing surgery at a HVH was associated with improved OS. Patients who completed surgery at HVHs had earlier stage disease and more commonly received adjuvant radiation when appropriate. Processes of care at HVHs should be identified to improve outcomes in all settings.