Ruddy, KJ

Abstract Background: Women younger than 40 generally fall outside the routine screening population for breast cancer (BC). We aimed to understand factors influencing diagnosis and treatment delays in these patients, and the impact of delays on disease-free survival (DFS). Methods: We included women aged ≤ 40 years at diagnosis of stage 0-IV BC enrolled in the Young Women’s BC Study from 2006-2016. Sociodemographics, initial BC symptoms, and disease status were collected via annual surveys. Medical record review was used to capture tumor characteristics and recurrence status. We used logistic regression to estimate associations between patient and tumor factors and three delay types: (1) self-delay (≥ 90 days from first symptom to presentation to a provider), (2) diagnosis delay (≥ 90 days from healthcare visit to diagnosis), and (3) treatment delay (≥ 60 days from diagnosis to first treatment). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated in multivariable models after choosing factors via backwards selection (p≤0.05 retained). Hazard ratios (HR) and 95% CIs for the association between delays and DFS, overall and by stage, were estimated via Cox proportional hazard models, adjusted for tumor and treatment factors. Time to event was measured from diagnosis or treatment to recurrence, death, or last follow-up, whichever occurred first. Results: Of 1,297 patients, 1,071 who completed the long-form baseline survey were included. Median time from first symptom to presentation was 14 days (interquartile range (IQR)=2-45), presentation to diagnosis was 14 days (IQR=7-30), and diagnosis to treatment was 41 days (IQR=25-57). Overall, 14% (n=153) had a self-delay and 11% (n=120) had a diagnosis delay. Of 839 patients with self-detected tumors, 18% had a self-delay and 13% had a diagnosis delay. Among those with Stage 1-3 BC (N=928), 22% (n=205) had a treatment delay. In univariable models, income <50K (p=0.01), lower financial comfort (p=0.01), and not living with a partner (p=0.03) were associated with higher odds of self-delay, while pregnancy within 1 year pre-diagnosis (p=0.05) and first-degree family history of any cancer (p=0.04) or BC (p=0.03) were associated with lower odds. Self-delays were more likely for women diagnosed with stage 4 BC (p=0.004) or with HER2+ tumors (p=0.03) and less likely for those with triple negative (TN) BC (p<0.001). In the multivariable model, family history of BC (OR=0.40, 95% CI=0.17-0.80), income <50K (OR=1.97, 95% CI=1.22-3.13) and TN subtype (OR v. luminal A=0.30, 95% CI=0.13-0.60) remained associated. Odds of diagnosis delay were higher among women who were younger (p=0.01) or with Stage 4 BC (p=0.004), and lower for those with luminal B (p=0.04), TN (p=0.01), or high grade tumors (p=0.03). In the multivariable model, younger age (OR per 1-year=0.94, 95% CI=0.89-0.99), and subtype (luminal B v. A OR=0.60, 95% CI=0.38-0.95; TN v. luminal A OR=0.35, 95% CI=0.16-0.70) remained associated. Multivariable models for self-and diagnosis delays remained similar when restricted to self-detected patients.Treatment delays were less likely among unemployed individuals (p=0.001), and women with a positive germline BC risk variant (p=0.002), luminal B (p=0.005) or TN (p<0.001) subtypes, and high-grade tumors (p=0.03). Only tumor factors remained significant in the multivariable model, including subtype (luminal B v. A OR=0.59, 95% CI=0.41-0.86, TN v. luminal A OR=0.25, 95% CI=0.13-0.43), and stage (stage 3 v. 1 OR=0.37, 95% CI=0.20-0.65). Overall and by stage at diagnosis, delays were not statistically significantly associated with DFS before or after adjusting for tumor and treatment factors. Conclusions: Delays in breast cancer care are influenced by multiple psychosocial and clinical factors, and disparities exist by socioeconomic status. It is critical to decrease self- and diagnosis delays to prevent stage 4 breast cancer. Citation Format: B. X. Zhang, T. Sella, Y. Zheng, G. J. Kirkner, K. J. Ruddy, S. M. Rosenberg, V. F. Borges, L. Schapira, S. E. Come, J. Peppercorn, A. H. Partridge, K. D. Brantley. Delays in breast cancer diagnosis and treatment in young women [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-16.

Abstract Background: Smoking, a known risk factor for numerous cancers, negatively impacts long-term survival in breast cancer (BC) survivors (Parada H Jr et al., 2017; Pierce et al., 2019). This study aims to characterize baseline smoking behaviors among breast cancer patients who self-reported smoking during an initial survey. Objectives: To assess attributes of patients self-reporting as current smokers near BC diagnosis, examining demographics, habits, quality of life, cancer treatments, comorbidities, and finances. Methods: Patients with newly diagnosed BC seen at Mayo Clinic Rochester between 2014-2024 were invited to enroll in the Mayo Clinic Breast Disease Registry. Consenting participants who completed self-reported questionnaires at baseline were included in this study. Smoking status and related variables at the time of survey completion were assessed via a baseline questionnaire, classifying participants as current, former, or never smokers. Of 3,959 participants completing baseline surveys, 3,729 were analyzed after excluding 103 with missing smoking data and 127 with their baseline survey returned >1-year post-diagnosis. Categorical variables were summarized with frequencies and percents, continuous variables with distributional statistics. Univariable associations with current smoking were assessed via two-sample t-tests (continuous) and chi-square or Fisher exact tests (categorical). Significant variables (p<0.05) were included in a multivariable logistic regression model. Results: Among 3,729 BC patients (mean age 58.3 years, SD 12.9), 99.1% were female, 97.1% White, and 98.7% non-Hispanic. Only 2.7% reported financial difficulty, 56.4% had a bachelor's degree or higher, 81.7% were married or equivalent, and 21.7% consumed ≥5 alcoholic drinks/week. Tumor stage distribution was as follows: Stage 0 (13.9%), Stage 1 (43.9%), Stage 2 (28.9%), Stage 3 (8.9%), and Stage 4 (4.5%); 33.8% received chemotherapy, 56.5% radiotherapy, 63.6% endocrine therapy, and 42.2% underwent mastectomy. Current smokers (2.6%, n = 95) had a median diagnosis age of 59.1 (IQR 31.8-87.1),with 32.6% consuming ≥5 drinks/week (vs. 21.5% in non-smokers, univariable p = 0.012), 69.5% with less than a Bachelor’s degree (vs. 42.9%, p<0.001), 9.6% facing financial difficulty (vs. 2.5%, p<0.001), and 10.5% diagnosed within 270-365 days after survey return (vs. 4.2%, p = 0.022). Tumor stage showed 47% with Stage 1 (vs. 43.7%, p = 0.245); 33.7% received chemotherapy, 60.0% radiotherapy, and 58.9% endocrine therapy. Current smokers had a mean smoking initiation age of 19.9 (SD 6.2), smoked 12.5 cigarettes/day (SD 7.9) for 32.8 years (SD 14.1), with mean 22.3 pack-years (SD 17.2).Univariable associations of demographic and clinical characteristics with current smoking showed Compared to never or former smokers, current smokers at the time of survey took a longer time to return their baseline survey (p = 0.022), were more likely to consume five or more alcoholic drinks per week (p = 0.012), were more likely to have difficulty paying their bills (p<0.001) and were less likely to obtain a Bachelor's degree or higher (p<0.001). These associations remained significant after multivariable adjustment. Conclusion: Current smoking (2.6%) soon after a BC diagnosis was independently associated with delayed survey return, higher alcohol use, financial difficulty, and lower education. Assessing smoking status and referring patients to smoking cessation programs are critical for addressing these risk factors and improving health outcomes. These findings highlight distinct socioeconomic and behavioral profiles among current smokers, suggesting potential targets for tailored interventions. Citation Format: S. Hirani, R. A. Vierkant, N. L. Larson, S. D. D’Andre, F. J. Couch, J. E. Olson, K. J. Ruddy. Identifying Smoking-Related Factors in Breast Cancer Patients: Mayo Clinic Registry Insight [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-04-18.

Abstract Background: Increasing rates of mastectomy, primarily bilateral mastectomy (BMx), have been most dramatic in young women with breast cancer (BC). Impact on long-term quality of life (QOL) is largely unknown. Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure, to women dx with BC at age ≤40 in a large prospective cohort study. Demographic and treatment information was obtained by surveys and chart review. Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by surgery types; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q domain scores. Results: 581 women with stage 0-3 BC completed the BREAST-Q a median of 5.8 years from dx. Median age at dx was 37 (range: 26-40) years; 86% had stage 0, 1 or 2 disease; 28% had breast-conserving surgery (BCS); 72% had mastectomy (Mx), among whom 72% underwent BMx and 89% had reconstruction. Mean BREAST-Q scores (unadjusted) for breast satisfaction, psychosocial, and sexual well-being were lower for patients having unilateral mastectomy (UMx) or BMx compared to BCS; physical function was similar among groups. In multivariate analysis, lower BREAST-Q psychosocial scores were associated with radiation and Mx (UMx or BMx). Lower sexual well-being scores were also associated with Mx. Lower satisfaction with breast scores following radiation were of a clinically significant magnitude (β -8.1 95% CI -11.9- -4.3, p-value 0.03). Lower scores for physical well-being were seen for patients reporting lymphedema and higher for those who had undergone surgery more than 5 years prior. Lower scores across all 4 domains were associated with reported financial distress. BREAST-Q domain mean scores (SD) BMxUMxBCSp-valueBreast satisfaction60.3 (18.9)59.5 (21.3)65.9 (20.7)0.008Physical well-being78.6 (14.9)79.7 (15.1)78.9 (15.5)0.8Psychosocial well-being68.1 (20.8)70.5 (21.2)76.1 (20.5)<0.001Sexual well-being48.6 (21.3)53.2 (21.7)57.5 (18.7)<0.001SD Standard deviation Conclusion: Local therapy in young breast cancer survivors may have a persistent impact on their breast satisfaction, psychosocial, and sexual outcomes, with particular effects from UMx or BMx. Socio-economic stressors also appear to play a role. When counseling young women about their surgical decisions, knowledge of potential long-term QOL impact is of critical importance. Citation Format: Dominici LS, Hu J, King TA, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Partridge AH, Rosenberg SM. Local therapy and quality of life outcomes in young women with breast cancer [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 GS6-06.

Abstract 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.

Abstract Background: Synchronous bilateral breast cancer is rare, with reported incidence from 0.3-12%; the incidence and pattern of bilateral breast cancer among younger women is unknown. Here we report the incidence and phenotypes of bilateral breast cancer in women ≤40 years of age enrolled in the Young Women's Study (YWS) cohort. Methods: The YWS is a multi-center, prospective cohort study that enrolled women with newly diagnosed breast cancer at age ≤40 years from 2006-2016. Those with synchronous bilateral breast cancer (in-situ and/or invasive) formed our study cohort. Disease characteristics and treatment were obtained by medical record review. Central pathology review was performed to capture histologic features and categorize the tumor phenotype as either luminal A (hormone receptor (HR)+, HER2-, grade 1 or 2), luminal B (HR+, HER2+, or HER2- and grade 3), HER2-type (HR-, HER2+), or triple negative (TNC; HR/HER2-). Tumor phenotypes of bilateral breast cancers were compared and evaluated for concordance. Results: Among 1302 patients enrolled in the YWS, 20 (1.5%) patients presented with bilateral disease, with median age of diagnosis of 38 years (range 18-40). The majority of patients (13 (65%)) presented with unilateral symptoms and contralateral disease was identified on subsequent imaging. 12 (60%) reported a positive family history of breast cancer and 17 (85%) underwent genetic testing; resulting in the identification of 6 mutation carriers (2 BRCA1, 3 BRCA2, 1 TP53). The majority of patients (15 (75%)) underwent bilateral mastectomy, 1 underwent unilateral mastectomy with contralateral lumpectomy, and 4 underwent bilateral lumpectomy. On pathology, 2 patients had bilateral in-situ disease, 5 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, all had concordant tumor histology (92% ductal, 8% ductal and lobular), 10 (77%) patients had bilateral luminal tumors and when fully characterized 6 were of the same luminal type. Only one patient had bilateral basal-like breast cancer. Patient ID ERPRHer2 amplifiedGradePhenotype1Left++-2Luminal A Right++-3Luminal B3Left++-3Luminal B Right++-3Luminal B6Left++-3Luminal B Right++-3Luminal B9Left++-2Luminal A Right++-2Luminal A10Left+++3Luminal B Right++-2Luminal A12Left+--3Luminal B Right+--2Luminal A13Left---NABasal-like Right++-NALuminal A or B14Left+++2Luminal B Right++-3Luminal B15Left++-3Luminal B Right+++3Luminal B16Left+++3Luminal B Right--+NAHEr2-type17Left---3Basal-like Right---3Basal-like19Left++-2Luminal A Right++-3Luminal B20Left++-1Luminal A Right++-2Luminal A Conclusions: Among a large cohort of young women, only 20 (1.5%) had bilateral disease, and the majority of the invasive tumors were of the luminal phenotype, yet frequently differed by grade or HER2 status; supporting the need for thorough pathologic evaluation of bilateral disease to determine risk and tailor treatment. Overall the low incidence of bilateral disease and preponderance of the luminal phenotype in this population is reassuring. Citation Format: Pak LM, Rosenberg SM, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Snow C, Collins L, King TA, Partridge AH. Tumor phenotype and concordance in synchronous bilateral breast cancer in young women [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 P6-22-03.

Abstract Background: The live attenuated non-pathogenic Edmonston MV vaccine strain has advantages as an oncolytic platform given its tumor specificity, potent bystander effect, and ability to be engineered and retargeted. MV-NIS expresses the human thyroidal sodium-iodide symporter (NIS) and is selectively oncolytic, entering tumor cells through CD46 (overexpressed on many cancers, including breast cancer of all subtypes) and Nectin-4. NIS expression in MV-NIS infected cells permits noninvasive monitoring of virus spread by SPECT-CT imaging of Tc-99m pertechnetate or I-123 uptake. Methods: NCT01846091 is a standard 3+3 phase I trial of a single IT administration of MV-NIS in pts with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) or metastatic breast cancer (MBC). Primary objectives are (a) safety and tolerability and (b) maximally tolerated single dose. The secondary clinical objective is to preliminarily assess antitumor efficacy at and away from the MV injection site. Key eligibility criteria were: absence of standard therapy with life prolonging intent; at least one lesion >1 cm amenable to percutaneous injection; and no impending visceral crisis. MV-NIS was administered on D1 with mandatory SPECT-CT at baseline (BL) and on D3&D8; repeat SPECT-CT on D15&D21 if the prior result was positive; mandatory tumor biopsies on D3&D21; optional tumor biopsies on D8&D15; assessments for viremia and viral shedding at BL and on D3,D8,D15,D21; and standard imaging for restaging at BL,D21,W6,W12. Results: Accrual completed with 12 evaluable pts (6 SCCHN and 6 MBC) at 3 dose levels (108, 3x108, 109 TCID50). The MBC group included 5 HR+/HER2- pts and 1 pt with mixed HR+/HER2- and HR+/HER2+ disease. 5 pts had evidence of disease progression prior to study participation. No dose limiting toxicities were observed among the MBC pts; AEs possibly related to MV-NIS in this group were gr2 fatigue, gr1 flu-like illness, gr2 lymphopenia (all n=1). No SCCHN responses were observed. Best response for the MBC pts was: stable disease (SD) >6 wks, n=4; clinical response, n=1; progression, n=1. One MBC pt with SD for 12 wks had positive SPECT/CT imaging at and away from the injection site on D3&D8 and was the only pt seronegative for measles IgG antibodies prior to MV-NIS exposure. The MBC pt who responded after initial MV-NIS exposure was the only pt with low viral RNA in blood (D3); she received additional doses at W9&W13 without toxicity through an expanded access protocol exemption and had disease progression by W19. No viral shedding was detected from mouth rinse or urine in any pt. MV was detected in tumor samples from all pts treated at the highest dose level. Additional blood and tissue analyses are in progress. Conclusion: These results demonstrate the safety of IT MV-NIS administration, provide early evidence of biologic activity in MBC, and support the possibility of viral replication in tumors remote from the IT injection site. A MV strain encoding the immunomodulatory neutrophil activating protein transgene has been constructed (MV-s-NAP) with preclinical evidence of improved antitumor activity and immunogenicity. The phase I MV-s-NAP trial will start recruitment in Fall 2018. Citation Format: Liu MC, Peng K-W, Federspiel MJ, Russell SJ, Brunton BA, Zhou Y, Packiriswamy N, Hubbard JM, Loprinzi CL, Peethambaram PP, Ruddy KJ, Allred JB, Galanis E, Okuno SH. Phase I trial of intratumoral (IT) administration of a NIS-expressing derivative manufactured from a genetically engineered strain of measles virus (MV) [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 P6-21-03.

Abstract Background: Male breast cancer (MBC) is rare, and usually managed by extrapolation from female breast cancer. We report on the characteristics and survival outcomes of MBC patients from Mayo Clinic Rochester (MCR). Methods: Medical records of MBC patients treated at MCR during a 25-year period (1990-2015) were reviewed. Demographic variables, tumor characteristics, recurrences, and overall survival (OS) were collected. Progression free survival (PFS) and OS were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of OS. Results: One hundred sixty-seven patients were included in the final analysis, with a median follow-up of 58 months after diagnosis. Baseline characteristics are presented in Table 1. Eighty percent of patients with ER-positive tumors received endocrine therapy. Among men with stage I-III disease, approximately 90% underwent mastectomy, and 44% received adjuvant chemotherapy. The 5-year locoregional and distant recurrence rates for patients with stage I-III disease were 4.4% and 21.5%, respectively. The 5-year PFS and OS for patients with stage I-III disease were 65.5% and 80.1%, respectively. In a multivariate analysis assessing predictors of OS in patients with stage I-III disease, older age (HR 1.05; 95% CI: 1.02 – 1.09), stage II (HR 11.06; 95% CI: 3.84 – 31.85) or stage III disease (HR 14.74; 95% CI (3.99 – 54.45), and omission of surgery (HR 45.33; 95% CI: 3.97 – 517.32) were associated with poorer OS, while endocrine therapy (HR 0.21, 95% CI: 0.09 – 0.51) was associated with better OS. ER, PR, HER2 and grade were not independently prognostic. The median OS for stage IV patients was 10 months, though this 11-man cohort was too small to allow assessment of prognostic factors in advanced male breast cancer. Conclusions: MBC remains an understudied condition. Prognostic factors in this stage I-III disease are consistent with those identified in other MBC retrospective cohorts. Prospective studies are needed to better understand the unique clinical features of MBC, and to improve outcomes, particularly for advanced disease. Table 1:Baseline characteristics N=167 Median age at diagnosis (Years)64.4 Ethnicity/Race: Caucasian131 (78.4%)African American4 (2.4%)Other or unknown32 (19.2%) Overall AJCC 7th edition stage: Stage I39 (23.4%)Stage II80 (47.9%)Stage III32 (19.2%)Stage IV11 (6.6%)Unknown5 (3.0%) Grade: 18 (4.8%)247 (28.1%)3101 (60.5%)Unknown12 (7.1%) ER status: Negative8 (4.8%)Positive153 (91.6%)Unknown6 (3.6%) PR status: Negative17 (10.2%)Positive141 (84.4%)Unknown9 (5.4%) HER-2 status: Negative70 (41.9%)Positive12 (7.2%)Unknown85 (50.9%) Citation Format: Yadav S, Leon-Ferre RA, Jimenez RE, Hawse JR, Hieken TJ, Couch FJ, Boughey JC, Ruddy KJ. Clinical characteristics and survival of patients with male breast cancer: The Mayo Clinic experience [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 P6-19-05.

Abstract Cyclin dependent kinase 4 and 6 inhibitors (CDK4/6i) are standard first line (1L) and second line (2L) treatments of ER+ MBC. However, the optimal treatment strategy after progression on a CDK 4/6i is unknown. Given concern for rapid disease progression after discontinuation of CDK4/6is (Bashour, J Cancer 2017), further data on responses to subsequent lines of therapy post CDK4/6i are needed. We performed a single institution retrospective review of patients (pts) with ER+ MBC who received 1L or 2L CDK4/6i to examine the prescribing patterns and clinical responses to post-CDK4/6i treatment. Methods: We identified 136 ER+ MBC pts prescribed a CDK4/6i at Mayo Clinic Rochester (from 12/2014 to 2/2018) on 1L or 2L who received at least 30 days of therapy and ≥ two clinic visits during treatment. For the 1L and 2L cohorts we assessed the time to treatment failure during (TTF-1) and after CDK4/6i therapy (TTF-2). TTF was defined as time from start of therapy to discontinuation for any cause. Additionally, we assessed overall survival (OS) post CDK4/6i discontinuation (defined as the date of TTF-1 to death or last follow up). Results: The study cohort included 81 and 55 pts treated with 1L and 2L CDK4/6is, respectively. In the 1L cohort, palbociclib/letrozole (82.3%) and palbociclib/fulvestrant (13.6%) were most commonly prescribed. Treatment was discontinued in 39/81 pts due to: progression (84.6%), intolerability (7.7%), and other (7.7%). The median TTF-1 was 19.7 mo (95% CI 11.2 – 25.4 mo). Subsequent treatment and response data were available in 37/39 pts that progressed on 1L CDK4/6i. The most commonly prescribed regimens included single-agent hormonal therapy (29.7%), everolimus/exemestane (27.0%), and single agent chemotherapy (21.7%). The overall median TTF-2 were as follows: everolimus/exemestane 13.2 mo [95%CI 0.33 mo – not reached (NR)]; single agent hormonal therapy 3.1 mo (95%CI 1.4 – 5.4 mo); and single agent chemotherapy 4.1 mo (95%CI 1.4 - 5.4 mo). With a median post-CDK4/6i follow up of 11.2 mo, we observed 8 deaths and the median OS-post CDK4/6i was NR. In the 2L cohort, common regimens were palbociclib/letrozole (63.6%) and palbociclib/fulvestrant (27.3%). Treatment was discontinued in 30/55 pts due to: progression (73.3%), intolerability (13.3%), and other (13.3%). The median TTF-1 in the 2L cohort was 8.3 mo (95%CI 4.6 – 12.7 mo). Subsequent treatment data were available in 24/30 pts and included single-agent hormonal therapy [n=7 (29.2%); median TTF-2 4.7 mo; 95%CI 1.9 – 14.0 mo], everolimus/exemestane [n=6 (25.0%); median TTF-2 3.2 mo, 95% CI 0.8-10.1 mo)] and single agent chemotherapy [n=6 (25.0%); median TTF-2 2.6 mo; 95%CI 1.7 mo – NR)]. With a median post-CDK4/6i follow up 18.7 mo in the 2L cohort, we observed 11 deaths, and the median OS-post CDK4/6i was 11.8 mo (95%CI 11.8 mo – NR). Conclusions: Single and combination-based endocrine strategies are commonly administered post-CDK4/6i without clinical evidence for rapid deterioration. The observation of a median treatment duration lasting >12 months in patients receiving everolimus/exemestane post-CDK4/6i supports ongoing studies evaluating drugs that target PI3K/mTOR pathway in combination and following progression on a CDK4/6i. Citation Format: Giridhar KV, Choong GM, Leon-Ferre RA, O'Sullivan CC, Ruddy KJ, Haddad TC, Hobday TJ, Peethambaram PP, Moynihan TJ, Loprinzi CL, Liu MC, Suman VJ, Goetz MP. Clinical management of metastatic breast cancer (MBC) after CDK 4/6 inhibitors: A retrospective single-institution 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 P6-18-09.

Abstract Background: The 21-gene Recurrence Score (RS) assay is prognostic among women with early-stage estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) and is used to select patients for chemotherapy (CT). Young women (age <40) have represented a minority in studies evaluating gene expression assays, including TAILORx, and additional data in young women are needed. Methods: In the Young Women's Breast Cancer Study, a prospective cohort study of women diagnosed with BC at age <40 enrolling between 2006-2016 (N=1302), we identified those with stage I-III ER+/HER2- BC. Disease and treatment information were obtained through serial surveys and medical record review. The RS was performed on banked specimens for those not tested clinically. Distant recurrence free interval (DRFI), defined as distant recurrence or BC specific death, by risk group was assessed using Cox regression and Kaplan-Meier survival estimates. Outcomes by receipt of CT were explored in the RS 11-25 group, and due to small number of events, reported descriptively. Results: Among eligible women (N=577), 189 (33%) had undergone RS testing and 320 (56%) had banked specimens sufficient for testing. Median follow-up was 6 years. Median age at diagnosis was 37, most had N0 BC (300/509, 59%), and the majority had RS 11-25 (306/509, 60%). RS result was significantly associated with DRFI in N0 BC, with hazard ratio (HR) (95% CI) of 0.29 (0.07,1.30) and 0.21 (0.09,0.50) for RS<11 and RS 11-25, respectively, relative to RS>26 (and trended towards significance in N1 BC). Results were similar using conventional RS groups. Among women with N0 BC and RS 11-25, 44% received CT, with two events in the 86 receiving CT (2.3%) and 6 events in the 109 without CT (5.5%); 5/8 (63%) occurred in those with RS 20-25. Table 1 N0N1Total Cohort N%N%N% 3005916332509100Median Age37.137.537.2Tumor Stage T120869694229358T28227784817635T3103159357T4001151Grade I4716855711II16555794926652III8829754618536Not assessed 1 1 PR status by IHC Negative (<1%)2071710398Positive (>=1%)280931469047092Chemotherapy No1414712715430Yes159531519335570Ovarian Suppression No263881499145289Yes37121495711TAILORx RS Groups RS <1133111495411RS 11-2519565885430660RS >=267224613714929Conventional RS Groups RS <1812742543319939RS 18-3012542694221142RS >=31481640259919 Table 2 6-year freedom from distant recurrence or breast cancer deathDRFI HR (95% CI) N0N1N0N1TAILORx RS Groups RS <1194.4%92.3%0.29 (0.07,1.30)0.21 (0.03,1.61)RS 11-2596.9%85.2%0.21 (0.09, 0.50)0.55 (0.27,1.12)RS >=2685.1%71.3%RefRefConventional RS Groups RS <1897.5%85.9%0.19 (0.06,0.59)0.31 (0.13,0.74)RS 18-3093.1%87.3%0.39 (0.16,1.00)0.32 (0.14,0.73)RS >=3186.4%62.8%RefRef Conclusions: The RS is prognostic among young women with node-negative and node-positive BC, and is a valuable tool for risk stratification. Disease outcomes among young women with N0 disease and RS 11-25, a minority of whom received CT, are very good. Evaluation of the effect of ovarian suppression/CT-induced amenorrhea by RS/treatment strata is ongoing. Citation Format: Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Jakubowski DM, Russell C, Winer EP, Partridge AH. Prognostic impact of the 21-gene recurrence score assay among young women with node-negative and node-positive ER+/HER2- breast cancer [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 P2-08-07.

Abstract Background: Chemotherapy can damage the ovaries and cause amenorrhea, a surrogate for infertility. Young women often wish to understand and minimize their risk of chemotherapy-related amenorrhea (CRA). However, the incidence of CRA with regimens that do not include either an anthracycline or cyclophosphamide is poorly studied. For patients with HER-2 positive disease, these anthracycline and cyclophosphamide-sparing regimens (e.g., docetaxel-carboplatin) are common (in combination with Her-2 directed therapy) in both the neoadjuvant and adjuvant settings. Methods: Women diagnosed with breast cancer under age 50 and within the past 10 years were recruited through a Dr. Susan Love Research Foundation Army of Women e-mail blast. Those who provided their contact information were mailed a consent form and medical record authorization form. Participants then received a web-based survey that inquired about receipt of and type of chemotherapy (including date of last dose) and date of last menstrual period (LMP). Patient-reported LMP was compared to date of final chemotherapy dose to determine if the LMP occurred before (defined as “CRA”) or after the last chemotherapy dose. When available, medical record data was used in place of survey data regarding type of chemotherapy used. Exclusion criteria included: LMP prior to diagnosis date, receipt of multiple chemotherapy regimens or no chemotherapy regimens, receipt of ovarian suppression medications (which interfere with interpretation of menstrual data), surgical menopause prior to or at the same time as diagnosis, a cancer diagnosis more than 10 years prior, incomplete menstrual data on the survey, report of an unknown chemotherapy regimen, and no date available for the last chemotherapy dose without an LMP within a month prior to survey completion. Fisher Exact test was used to compare CRA rates between regimens. Rates after two anthracycline-sparing regimens (taxane/cyclophosphamide; taxane/carboplatin) were compared to rates after anthracycline/cyclophosphamide/taxane. Results: 273 women consented to participate in this study, 258 of whom filled out the web survey. 151 of them were eligible for this analysis with a median age at diagnosis of 41 (range 24-49) and a median time from last chemotherapy dose to survey of 62.5 months (range 2-138). CRA occurred in 51.2% of the 86 participants who received an anthracycline, cyclophosphamide, and a taxane, in 41.9% of the 43 participants who received only a taxane and cyclophosphamide (p=0.35), and in 13.3% of the 15 participants who received carboplatin with a taxane (p=0.01). When the 11 patients who were <12 months since last chemotherapy were excluded, CRA rates changed minimally. Age did not differ by regimen, but median time since chemotherapy was shorter in the taxane/carboplatin group (35 months vs. 68 months). Trastuzumab with or without pertuzumab was administered in 100% of patients who received carboplatin/taxane, in 23.3% of patients who received taxane and cyclophosphamide, and in 22.1% of patients who received anthracycline/cyclophosphamide/taxane. Conclusions: This study suggests that carboplatin/taxane may be substantially less gonadotoxic than cyclophosphamide-based (neo)adjuvant regimens. Further research is necessary to confirm these findings. Citation Format: Gast KC, Cathcart-Rake EJ, Norman A, Eshragi L, Obidegwu N, Yost K, Nichols HB, Rosenberg S, Su HI, Stewart E, Couch F, Vachon C, Ruddy KJ. Regimen-specific rates of chemotherapy-related amenorrhea in breast cancer survivors [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 P1-12-10.