Faculty Bibliography

OBJECTIVE:The real-world management of patients with non-BRCA, homologous recombination repair pathway variants with increased or uncertain risks of ovarian cancer is unknown. The objective was to determine the adoption of risk-reducing salpingo-oophorectomy (RRSO) for carriers of variants with increased or uncertain risks of ovarian cancer beyond BRCA. METHODS:This was a retrospective cohort study of patients at three hospitals with non-BRCA, homologous recombination repair pathway variants with increased risk (BRIP1, RAD51C, RAD51D) and uncertain risk (ATM, BARD1, NBN, PALB2) of ovarian cancer. Outcomes of interest were adoption of RRSO and factors associated with adoption of RRSO. Wilcoxon rank-sum, chi-square, and logistic regression were performed with p < 0.05. RESULTS:Of 318 patients, 76 (24%) had pathogenic variants with increased risks of ovarian cancer (BRIP1, 45; RAD51C, 20; RAD51D, 11), and 242 (76%) had variants with uncertain risks of ovarian cancer (ATM, 145; PALB2, 69; NBN, 23; BARD1, 5). Of 64 patients eligible for RRSO by National Comprehensive Cancer Network (NCCN) criteria or family history, 31 (48%) underwent RRSO. Among eligible patients who did not undergo RRSO, 24 (73%) were not referred for gynecologic oncology consultation. Older age at testing (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.03-1.13) and referral to gynecologic oncology (aOR 33.48, CI 8.10-138.39) were associated with increased adoption of RRSO when adjusting for personal and family history of breast and ovarian cancer. CONCLUSION/CONCLUSIONS:Half of RRSO-eligible patients by NCCN criteria beyond BRCA did not undergo RRSO. Opportunities exist for improving education to increase referrals to facilitate RRSO for these patients.

BACKGROUND:In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy (RRSO) has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network (NCCN) recommends that patients with BRCA mutations undergo RRSO between the ages of 35-40 years for BRCA1 mutation carriers and between the ages of 40-45 years for BRCA2 mutation carriers, or after childbearing is complete. Currently, uptake and timing of RRSO and reasons for delays in RRSO are not well understood. OBJECTIVE:We sought to evaluate uptake and timing of RRSO among women with BRCA1/2 mutations in relation to NCCN guidelines, and reasons for delays in RRSO. STUDY DESIGN/METHODS:In this retrospective chart review, we identified women with BRCA1/2 mutations who discussed RRSO with a provider between 2012 and 2021. Uptake of RRSO was documented, and patients were classified as having timely or delay in RRSO based on NCCN guidelines. For those with delay in RRSO, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed RRSO. A multivariable logistic regression model was used to evaluate the associations between factors related to timing of RRSO. RESULTS:We identified 638 BRCA1/2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone RRSO and 332 (52.0%) had not. When evaluating timing of RRSO, 136 (21.3%) underwent timely RRSO, 239 (37.5%) had delay in RRSO, and 263 (41.2%) had not undergone RRSO but were younger than NCCN age guidelines so were neither timely nor delayed. Patients with delay in RRSO were significantly older at the time of genetic testing compared to those with timely RRSO (mean 49.8 vs 36.3 years; p < 0.001). Of the 306 patients who underwent RRSO, those with delayed RRSO had a significantly shorter interval between BRCA identification and RRSO compared to those with timely RRSO (median 8.7 vs 17.6 months; p < 0.001). Patients with delay in RRSO were more likely to have a personal history of cancer than those with timely RRSO (49.8% vs 37.5%; p=0.028). Of the 239 women with delay in RRSO, reasons included: 188 (78.7%) for delayed BRCA mutation identification; 29 (12.1%) for menopausal concerns; 17 (7.1%) for ongoing cancer treatment; 12 (5.0%) for coordination with breast surgery; 20 (8.4%) for miscellaneous reasons; and 19 (7.9%) with no reasons documented. In the multivariate model, older age at BRCA diagnosis (OR 0.73; 95%CI [0.68-0.78]; p<0.001) was significantly associated with delayed RRSO timing; those with BRCA2 mutation type were 7.54 times as likely to have timely RRSO compared to BRCA1 mutation carriers (OR 7.54; 95%CI [3.70-16.42]; p<0.001). CONCLUSION/CONCLUSIONS:Nearly 38% of BRCA1/2 mutation carriers undergo or have yet to undergo RRSO beyond the NCCN recommended age. The most common reason for delay in RRSO was delayed identification of BRCA mutation, noted in 79% of patients with delayed RRSO. Timely genetic testing for eligible patients can increase appropriately timed RRSO for prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.

Gender norms, roles and relations differentially affect women, men, and non-binary individuals' vulnerability to disease. Outbreak response measures also have immediate and long-term gendered effects. However, gender-based analysis of outbreaks and responses is limited by lack of data and little integration of feminist analysis within global health scholarship. Recognising these barriers, this paper applies a gender matrix methodology, grounded in feminist political economy approaches, to evaluate the gendered effects of the COVID-19 pandemic and response in four case studies: China, Hong Kong, Canada, and the UK. Through a rapid scoping of documentation of the gendered effects of the outbreak, it applies the matrix framework to analyse findings, identifying common themes across the case studies: financial discrimination, crisis in care, and unequal risks and secondary effects. Results point to transnational structural conditions which put women on the front lines of the pandemic at work and at home while denying them health, economic and personal security - effects that are exacerbated where racism and other forms of discrimination intersect with gender inequities. Given that women and people living at the intersections of multiple inequities are made additionally vulnerable by pandemic responses, intersectional feminist responses should be prioritised at the beginning of any crises.

SUMMARY/CONCLUSIONS:There remain significant gaps in the evidence-based care of patients undergoing gender-affirming mastectomy with regard to implications for breast cancer development and screening. The current clinical evidence does not demonstrate an increased risk of breast cancer secondary to testosterone therapy in transgender patients. Gender-affirmation mastectomy techniques vary significantly with regard to the amount of residual breast tissue left behind, which has unknown implications for the incidence of postoperative breast cancer and need for screening. Subcutaneous mastectomy should aim to remove all gross breast parenchyma, although this is limited in certain techniques. Tissue specimens should also be routinely sent for pathologic analysis. Several cases of incidental breast cancer after subcutaneous mastectomy have been described. There is little evidence on the need for or types of postoperative cancer screening. Chest awareness is an important concept for patients that have undergone subcutaneous mastectomies, as clinical examination remains the most common reported method of postmastectomy malignancy detection. In patients with greater known retained breast tissue, such as those with circumareolar or pedicled techniques, consideration may be given to alternative imaging modalities, although the efficacy and cost-utility of these techniques must still be proven. Preoperative patient counseling on the risk of breast cancer after gender-affirming mastectomy in addition to the unknown implications of residual breast tissue and long-term androgen exposure is critical. Patient awareness and education play an important role in shared decision-making, as further research is needed to define standards of medical and oncologic care in this population.

The coronavirus disease 2019 (COVID-19) pandemic poses particular challenges for migrant workers around the world. This study explores the unique experiences of foreign domestic workers (FDWs) in Hong Kong, and how COVID-19 impacted their health and economic wellbeing. Interviews with FDWs (n = 15) and key informants (n = 3) were conducted between May and August 2020. FDWs reported a dual-country experience of the pandemic, where they expressed concerns about local transmission risks as well as worries about their family members in their home country. Changes to their current work situation included how their employers treated them, as well as their employment status. FDWs also cited blind spots in the Hong Kong policy response that also affected their experience of the pandemic, including a lack of support from the Hong Kong government. Additional support is needed to mitigate the particularly negative effects of the pandemic on FDWs.

PURPOSE/OBJECTIVE:Food insecure cancer patients experience worse health outcomes and poorer quality of life than food secure patients. There has been little research in programs to alleviate food insecurity in cancer patients. The objective of this paper is to report on the food purchasing behaviors of cancer patients enrolled in a supplemental food voucher program. METHODS:This paper utilized data from a three-arm randomized controlled trial investigating the impact of food interventions on alleviating food insecurity in cancer patients receiving chemotherapy and/or radiation therapy. In one arm, patients received a monthly $230 voucher with which to purchase food. Receipts were collected for items purchased with the voucher and were coded to analyze purchasing behaviors. RESULTS:Thirty-three patients provided receipts for more than 11,000 individual items. Patients spent 50% of voucher funds on animal protein, fruits, and vegetables. Patients spent, on average, 77% of voucher funds on items categorized as "healthy." CONCLUSIONS:Patients who received a food voucher purchased more fruits and vegetables than national averages would suggest. They also spent less on sweetened beverages than national samples. Patients who were born outside of the United States or who were limited English proficient purchased significantly more healthy foods than English-speaking and American-born study patients. Supplemental food vouchers for food insecure cancer patients resulted in the purchase of healthy food items.

OBJECTIVES/OBJECTIVE:Lynch syndrome (LS) accounts for the majority of inherited endometrial cancers (EC), and the identification of probands presents a unique opportunity to treat and prevent multiple cancers. The diagnosis of EC can provide the indication for women with specific risk factors to undergo genetic testing (GT). We sought to evaluate genetic counseling referrals (GCR) and subsequent GT rates in an ethnically diverse group of high-risk women. METHODS:All women diagnosed with EC between 2011 and 2016 were identified. Risk factors for LS including age, family and personal histories of Lynch-related cancers and loss of tumor mismatch repair (MMR) protein expression were identified from laboratory and medical records. Standard two-sided statistical tests were used. RESULTS:Of 583 women diagnosed with EC, 184 (31.6%) were found to have at least one high-risk characteristic for LS. Among these high-risk women, 58% were given GCR and resulting in only 35% undergoing GT. Ten of the 65 high-risk women who had GT (15.4%) were diagnosed with Lynch syndrome, and all ten met high-risk criteria. Two women of Asian race had tumors exhibiting retained MMR protein expression despite germline testing demonstrating Lynch syndrome. CONCLUSIONS:Many high-risk women do not receive GCR despite a high rate of germline mutations among these women. Improving GCR among high-risk women will lead to more subsequent GT to identify more Lynch syndrome families and prevent additional cancers. Among our ethnically diverse cohort, two women diagnosed with LS had retained MMR protein expression. GCR should be offered to women who possess high-risk characteristics despite normal MMR protein expression.

IntroductionEstrogen inhibition is effective in preventing breast cancer in only up to 50% of women with precancerous lesions and many experience side effects that are poorly tolerated. As insulin-like growth factor I (IGF-I) underlies both estrogen and progesterone actions and has other direct effects on mammary development and carcinogenesis, we hypothesized that IGF-I inhibition might provide a novel approach for breast cancer chemoprevention.MethodsIn total, 13 women with core breast biopsies diagnostic of atypical hyperplasia (AH) were treated for 10 days with pasireotide, a somatostatin analog which uniquely inhibits IGF-I action in the mammary gland. They then had excision biopsies. 12 patients also had proliferative lesions and one a ductal carcinoma in situ (DCIS). Primary outcomes were changes in cell proliferation and apoptosis after treatment. Expression of estrogen receptor (ER), progesterone receptor (PR), and phosphorylated Insulin-like growth factor I receptor (IGF-1R), protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2) were also assessed. Core and excision biopsies from 14 untreated patients served as non-blinded controls. Hyperglycemia and other side effects were carefully monitored.ResultsPasireotide decreased proliferation and increased apoptosis in all AH (from 3.6 inverted question mark+/- inverted question mark2.6% to 1.3 inverted question mark+/- inverted question mark1.2% and from 0.3 inverted question mark+/- inverted question mark0.2% to 1.5 inverted question mark+/- inverted question mark1.6%, respectively) and proliferative lesions (from 3.8 inverted question mark+/- inverted question mark2.5% to 1.8 inverted question mark+/- inverted question mark1.8% and from 0.3 inverted question mark+/- inverted question mark0.2% to 1.3 inverted question mark+/- inverted question mark0.6%, respectively). The DCIS responded similarly. ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly. In contrast, tissue from untreated controls showed no change in cell proliferation or phosphorylation of IGF-1R, AKT or ERK 1/2. Mild to moderate hyperglycemia associated with reduced insulin levels was found. Glucose fell into the normal range after discontinuing treatment. Pasireotide was well tolerated and did not cause symptoms of estrogen deprivation.ConclusionsIGF-I inhibition by pasireotide, acting through the IGF-1R, was associated with decreased proliferation and increased apoptosis in pre-malignant breast lesions and one DCIS. Assuming hyperglycemia can be controlled, these data suggest that inhibiting the IGF-I pathway may prove an effective alternative for breast cancer chemoprevention.Trial registration NCT01372644 Trial date: July 1, 2007.