This article presents an autobiographical account of an older woman's lived experience of selfemployment. Little is known about women who experience ongoing self-employment into their 50s and beyond. Shoshanna's personal narrative describes her experiences and the challenges she has faced as she reflects upon her attempts to grow and sustain her business and the implications of ageism and gender inequality in laying a claim to entrepreneurship. The narrative proceeds to reflect on her activist work, as it is constructed through the creation of a social enterprise to support older people. Shoshanna's narrative provides valuable insights into the intersection of age and gender in self-employment moving from discrimination to active support.

Background Young women are more likely than older women to present with higher stage breast cancer (BC) and may benefit to a greater extent from downstaging with neoadjuvant systemic treatment (NST). Young age is also associated with greater likelihood of pathologic complete response (pCR). Using a large prospective cohort of young women with BC, we investigated response to neoadjuvant therapy, eligibility for breast conserving surgery (BCS) pre- and post-NST, and surgical treatment. Methods The Young Women's Breast Cancer Study (YWS) is a multi-center cohort of women diagnosed with BC at age ≤40, that enrolled 1302 patients from 2006 to 2016. Disease characteristics and treatment information were obtained through medical record and central pathology review. Surgical recommendation before and after NST, conversion from BCS borderline/ineligible to BCS eligible, surgery, documented reasons for choosing mastectomy (MTX) among BCS eligible women, and final pathologic response were independently reviewed. Results Among 1302 women enrolled in YWS, 801 (62%) presented with unilateral stage I-III breast cancer and 317(40%) received NST. Median age was 36 years old (22-40). Pre-NST, 85/317 (27%) were BCS eligible, 49 (15%) were borderline, and 169 (53%) were not eligible (16 inflammatory breast cancer (IBC), 88 large tumor size /cosmetic, 48 diffuse calcifications, and 83 multicentricity). Among the 218 patients who were BCS ineligible/borderline pre-NST, 82 (38%) became eligible for BCS after NST. 4 patients who were BCS eligible pre-NST became ineligible. Of all patients eligible for BCS post-NST (n=163), 80 (49%) attempted BCS, 74 (93%) of whom were successful, and 83 (51%) chose MTX. Reasons for choosing MTX included: patient preference (38/83 (46%)), BRCA or TP53 mutation (31 (37%)), family history (3 (4%)), unknown (11 (13%)). On final pathology, 75 (24%) patients had pCR. Among patients who achieved a pCR, 48 (64%) underwent MTX, fewer than half (21/48 (44%)) were for anatomic indications (IBC, large tumor at diagnosis, diffuse calcifications, multicentric disease). Conclusion While NST doubled the proportion of young women eligible for BCS, nearly half chose MTX regardless of response to NST, mostly for personal preference or high-risk preventative reasons. These data highlight that surgical decision making among young women with breast cancer is often driven by factors beyond extent of disease and clinical response to therapy. Table 1.Clinical-pathologic characteristicsCharacteristicsNumber%Pre NST surgical recommendation  BCS eligible8526.8Borderline4915.5BCS ineligible16953.3Unknown144.4Clinical Response  Complete20263.7Partial9229.0Stable30.9Progressing72.2Unknown134.1Pathologic Response  pCR (No invasive or DCIS)7524No pCR24276Post NST Surgical recommendation  BCS eligible16351.4BCS ineligible14445.4Unknown103.2Attempted surgery  BCS8025.2MTX23674.1Unknown20.6Final Surgery  BCS7423.3MTX24176unknown20.6 Citation Format: Kim HJ, Dominici L, Rosenberg S, Pak LM, Poorvu PD, Ruddy K, Tamimi R, Schapira L, Come S, Peppercorn J, Borges V, Warner E, Vardeh H, Collins L, King T, Partridge A. Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-01.

Resistance exercise is deemed safe for women recovering from conventional breast cancer therapies but few clinicians are aware that dragon boat racing, as a form of resistive exercise, is available to the breast cancer community. The objectives of this study were to 1) increase clinician awareness of dragon boat racing (DBR) in breast cancer survivors as a community-based physical activity, and 2) evaluate quality of life (QOL) in breast cancer survivors with or without lymphedema who participate in DBR. This prospective, observational study surveyed 1,069 international breast cancer dragon boat racers from eight countries to compare function, activity, and participation in women with and without self-reported lymphedema using the Lymph-ICF questionnaire. Seventy-one percent of women (n=758) completed the questionnaires. Results revealed significantly higher Lymph-ICF scores in the lymphedema participants, signifying reduced QOL, when compared to the nonlymphedema participants (p<0.05), except for "go on vacation" for which no statistical difference was reported (p=0.20). International breast cancer survivors with lymphedema participating in DBR at an international competition had reduced function, limited activity, and restricted participation compared to participants without lymphedema. Clinicians should consider utilizing DBR as a community-based activity to support exercise and physical activity after a breast cancer diagnosis.

Background: Breast cancer (BC) may recur years to decades after initial treatment, leading to incurable, metastatic disease. Prior studies have shown blood biopsy can detect minimal residual disease (MRD), but not in all patients and often with very short lead time. Most efforts thus far have focused on tracking one or a few mutations via ctDNA, which may limit sensitivity. Here we sought to maximize the detection sensitivity of blood biopsies by tracking up to hundreds of individualized tumor mutations in cell-free DNA (cfDNA). Doing so enables us to break the detection ceiling imposed by the limited copies of each gene in the cell-free DNA in a blood draw. Methods: cfDNA was extracted from archival plasma samples (n=271) from 142 patients with stage 0-III BC enrolled prospectively onto two IRB-approved studies. We applied whole-exome sequencing (WES) to define up to several hundred mutations from each patient’s tumor. To limit potential errors, we employed strict criteria to select somatic SNVs to track using duplex sequencing in cfDNA. We required detection of ≥ 2 mutations for a cfDNA sample to be MRD+ and excluded any mutations also found in a patient’s own germline DNA. Results: We identified 142 patients treated for stage 0-III BC, who had postoperative blood and plasma samples available, and were monitored for distant recurrences for up to thirteen years. All patients had biopsy-proven BC, with 86 (61%) having HR+/HER2- BC, 31 (22%) having HR-/HER2-, or “triple negative” BC (TNBC), and 25 (18%) having HER2-positive disease. Three (2%) patients had stage 0 disease, 32 (23%) had stage I, 68 (42%) had stage II, and 39 (27%) had stage III BC at diagnosis. Archived plasma samples were collected post-operatively, at year 1, and at year 4. We created individualized assays targeting a median of 57 mutations (range 2 - 346) per patient. Reasoning that MRD status after completion of all local therapy and chemotherapy might best predict for distant recurrence, we conducted a landmark analysis at one year following surgery, and found all patients (n=6/6) with detectable MRD experienced recurrence (HR=21.2 (7.43-60.35)) in a median of 6.7 (range 3.4 - 15.8) months. Median lead time including all timepoints from first positive blood sample to recurrence was 18.9 (range: 3.4 - 39.2) months. Finally, in a multivariate model, MRD remained highly statistically significant independent of stage, subtype, and age at diagnosis. Conclusions: We present a novel approach to MRD tracking based on the premise that tracking many - rather than one or a handful of - mutations inherently increases sensitivity and that assay personalization maximizes sensitivity in a disease without multiple, recurrent mutations. To our knowledge, the lead time we show here is significantly longer than that seen in prior investigations, and if confirmed, could offer an opportunity to treat MRD long before the development of clinically apparent metastatic disease. Prospective studies are needed to determine whether earlier detection of MRD is clinically meaningful for patients. Citation Format: Heather A Parsons, Justin Rhoades, Sarah C. Reed, Greg Gydush, Priyanka Ram, Pedro Exman, Kan Xiong, Christopher Lo, Tianyu Li, Mark Fleharty, Greg Kirkner, Denisse Rotem, Ofir Cohen, Melissa Hughes, Shoshanna Rosenberg, Laura Collins, Kathy Miller, Brendan Blumenstiel, Carrie Cibulskis, Donna Neuberg, Samuel S. Freeman, Niall Lennon, Nikhil Wagle, Gavin Ha, Daniel G. Stover, Atish D. Choudhury, Gad Getz, Matthew Meyerson, Nancy U. Lin, Ian E. Krop, J. Christopher Love, G. Mike Makrigiorgos, Ann Partridge, Erika Mayer, Todd R. Golub, Viktor A. Adalsteinsson. Ultrasensitive detection of minimal residual disease in patients treated for breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-03.

Background: Hereditary breast cancer (HBC) comprises more than 10% of all breast cancers (BC). Mutations in the BRCA1/2 genes are found in approximately half of HBC patients. The majority of BRCA1 associated tumors are ER, PR and HER2 negative with basal-like expression pattern. BRCA2 associated tumors are mostly ER positive (ER+). In the present study we aim to further explore clinical and molecular characteristics of BRCA associated BC in 3 different cohorts. Methods: Three different BC databases (DB) were evaluated: (i) Hadassah oncogenetic BC DB (n=4429); (ii) Nick-Zainal et al. BC DB (n=560), and (iii) METABRIC BC DB (n= 1980). We tested for differences in age at diagnosis between BRCA positive (BRCA+) and BRCA negative (BRCA-) patients with either ER+ or ER negative (ER-) tumors. Point mutation analysis was performed in cohorts ii & iii and mRNA differential expression (DEA) and pathway analysis were performed in cohort iii, using Ingenuity Pathway Analysis (IPA). Results: Age (years) at diagnosis for cohorts i, ii,&iii respectively, for ER+ PT:BRCA1-44, NA, 60; for BRCA2-49, 48, 64; for BN – 53, 56, 63. For ER-: BRCA1-42, 42, 47; for BRCA2-48, 52, 49; for BN-49, 54, 56. For cohorts ii&iii, higher frequencies of TP53 and PIK3Ca mutations were found among BRCA+&BRCA-, respectively. DEA was performed between BRCA+&BRCA- in ER- tumors: the major activated pathways involved cancer related processes and were highly significant (up to p=1e-7.5, FDR=1e-4.5). Surprisingly - the most significant pathway was Estrogen Mediated S-phase Entry and the most activated upstream regulator was ERBB2. Similar evaluation in ER+ showed mostly differences in immune related pathways (differences not statistically significant). Conclusions: Younger age at presentation was observed in BRCA1 vs. BRCA2 patients. No age differences were observed between ER+&ER- PT in cohort i&ii, in cohort iii ER- BRCA+ Patients were younger than ER+ BRCA+ (similar age as ER+ BRCA-). BRCA+ show different mutational profile than BRCA-. ER+ BRCA+ and BRCA- show similar genomic characteristics. By contrast, for ER- BRCA+ differs markedly from BRCA-. This might imply that BRCA+ associated tumors consist of two genomically distinct subtypes: (i) ER-, and (ii) ER+. The results may shed light on possible somatic factors which affect the development of BC BRCA+ and carry preventive and therapeutic implications. Citation Format: Peretz TY, Zick A, Luna K, Grinshpun A, Sonneblick A, Iziely B, Hamburger TG, Cohen S, Granit AM, Dvir M, Rosenberg S. ER dependent breast cancer phenotype in BRCA 1/2 carriers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-03-02.