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Uptake and timing of risk-reducing salpingo-oophorectomy among patients with BRCA1/2 mutations

Smith, Maria J; Gerber, Deanna; Olsen, Anne; Khouri, Olivia R; Wang, Yuyan; Liu, Mengling; Smith, Julia; Pothuri, Bhavana
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.
PMID: 34171390
ISSN: 1097-6868
CID: 4925842

More than a public health crisis: A feminist political economic analysis of COVID-19

Smith, Julia; Davies, Sara E; Feng, Huiyun; Gan, Connie C R; Grépin, Karen A; Harman, Sophie; Herten-Crabb, Asha; Morgan, Rosemary; Vandan, Nimisha; Wenham, Clare
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.
PMID: 33705248
ISSN: 1744-1706
CID: 4819612

Oncologic Considerations for Safe Gender-Affirming Mastectomy: Preoperative Imaging, Pathologic Evaluation, Counseling, and Long-Term Screening

Salibian, Ara A; Axelrod, Deborah M; Smith, Julia A; Fischer, Beverly A; Agarwal, Cori; Bluebond-Langner, Rachel
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.
PMID: 33565823
ISSN: 1529-4242
CID: 4806412

"We also deserve help during the pandemic": The effect of the COVID-19 pandemic on foreign domestic workers in Hong Kong

Lui, Ingrid D; Vandan, Nimisha; Davies, Sara E; Harman, Sophie; Morgan, Rosemary; Smith, Julia; Wenham, Clare; Grépin, Karen Ann
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.
PMID: 33817682
ISSN: 2666-6235
CID: 4845342

Food Purchasing Behavior of Food Insecure Cancer Patients Receiving Supplemental Food Vouchers

Paolantonio, Luke; Kim, Soo Young; Ramirez, Julia; Roberts-Eversley, Nicole; Li, Yuelin; Melnic, Irina; Wu, Minlun; Jutagir, Devika R; Smith, Julia; Oladele, Modupe; Gany, Francesca
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.
PMID: 31828492
ISSN: 1433-7339
CID: 4485762

Missed opportunities: Genetic counseling and testing among an ethnically diverse cohort of women with endometrial cancer

Lee, Jessica; Gubernick, Lindsay R; Brodsky, Allison L; Fehniger, Julia E; Levine, Douglas A; Gerber, Deanna; Asgari, Shabnam A; Cantor, Anna; Martineau, Jessica T; Ginsburg, Ophira M; Smith, Julia A; Pothuri, Bhavana
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.
PMID: 30077346
ISSN: 1095-6859
CID: 3226372

Clinical Hereditary Cancer Syndromes and Gene Panel Testing [Editorial]

Sin, Danielle N; Smith, Julia A
ISSN: 0890-9091
CID: 2322392

Insulin-like growth factor-I inhibition with pasireotide decreases cell proliferation and increases apoptosis in pre-malignant lesions of the breast: a phase 1 proof of principle trial

Singh, Baljit; Smith, Julia A; Axelrod, Deborah M; Ameri, Pietro; Levitt, Heather; Danoff, Ann; Lesser, Martin; de Angelis, Cristina; Illa-Bochaca, Irineu; Lubitz, Sara; Huberman, Daniel; Darvishian, Farbod; Kleinberg, David L
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.
PMID: 25385439
ISSN: 1465-5411
CID: 1348822

Breast cancer chemoprevention by IGF-I inhibition in women with atypical hyperplasia of the breast: A phase 1/2 proof of principle trial [Meeting Abstract]

Kleinberg, David L; Axelrod, Deborah; Smith, Julia; Singh, Baljit; Lesser, Martin; Ameri, Pietro; Danoff, Ann; Bochaca, Irineu Illa; de Angelis, Cristina
ISSN: 1538-7445
CID: 1599312

Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer

Singh, Jasmeet; Novik, Yelena; Stein, Stacey; Volm, Matthew; Meyers, Marlene; Smith, Julia; Omene, Coral; Speyer, James; Schneider, Robert; Jhaveri, Komal; Formenti, Silvia; Kyriakou, Victoria; Joseph, Benson; Goldberg, Judith D; Li, Xiaochun; Adams, Sylvia; Tiersten, Amy
INTRODUCTION: Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) inhibitor) and carboplatin may have activity in metastatic triple-negative breast cancer (TNBC). METHODS: The primary objective of this study was to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting >/=6 months) and the toxicity of everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was allowed. Treatment consisted of intravenous carboplatin area under the curve (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with daily 5 mg everolimus. RESULTS: We enrolled 25 patients in this study. Median age was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was achieved in a patient progressing on single agent carboplatin. The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There were seven patients (28%) with >/= grade 3 thrombocytopenia; three (12%) with grade 3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3 anemia. Greater hematological toxicity was seen in the first seven patients treated with carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 4, the regimen was well tolerated with only one out of 18 patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia. There was only one case of mucositis. CONCLUSION: Everolimus-carboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC 4 was well tolerated in combination with everolimus with continuing responses. TRIAL REGISTRATIONS: NCT01127763.
PMID: 24684785
ISSN: 1465-542x
CID: 1583872