Ruddy, Kathryn J.

10065 Background: Prospective data regarding fertility and pregnancy after breast cancer are limited. Many young survivors are interested future fertility, but pregnancy rates among women attempting and not attempting pregnancy have not been studied prospectively. Methods: As part of a multicenter cohort study, women diagnosed age ≤40 with stage 0-3 breast cancer are surveyed at baseline then annually regarding fertility interest, attempts, and pregnancies. Chi-square tests were used to compare proportions attempting and achieving pregnancy. Results: At least once in the 5 years (yrs) after Dx, 334/959 (35%) women reported interest in future biologic children. The percent interested was stable in the first 3 yrs then declined: 256 (27%, baseline), 244 (27%, 1 year), 209 (25%, 2 yrs), 176 (25%, 3 yrs), 106 (18%, 4 yrs), and 72 (16%, 5 yrs). Pregnancy was attempted by 104/334 (31%) of women who reported interest and 4/625 (1%) who did not. Pregnancy occurred in 118 women (12%), including 76/108 (70%) who attempted and 42/851 (5%) who did not. Attempts and achieving pregnancy were associated with younger age, partnered status, and not having children prior to Dx (table). Lower stage was associated with attempting pregnancy and ER negative disease with achieving pregnancy. Conclusions: A substantial number of young women become pregnant in the 5 years after a breast cancer diagnosis. Given that over 1/3 of pregnancies were among women who did not report attempting, additional attention to contraception counseling should be considered. Further evaluation of assisted reproductive technology use, pregnancy and disease outcomes in this cohort, and the POSITIVE Trial (NCT02308085) will shed light on the feasibility and safety of pregnancy after breast cancer. [Table: see text]

e20092 Background: More than 5,000 premenopausal women are diagnosed (dx’d) with lung cancer annually in the United States. Improvements in treatment are contributing to a growing population of young survivors. Limited data exist regarding the risk of treatment-related amenorrhea, a surrogate for infertility and early menopause, after systemic therapies for lung cancer. Methods: Since 1997, we mailed annual surveys to patients seen at Mayo Clinic for lung cancer who consented to join a research cohort. Surveys queried menopausal status and age of menopause. Those who were dx’d under age 50, who were treated with curative intent, and who reported that they were premenopausal at the time of the cancer dx were included in this analysis. “Immediate” treatment-related menopause was defined as reporting age of menopause as the same as the age at diagnosis or 1 year (yr) older. Results: Of 182 survey respondents to date (mean time from dx to 1st survey: 26 mos, SD 24 mos, range 12-202 mos), 85 (mean age 44 yrs, SD 5, range 34-48) received chemo during the yr after diagnosis, 26 of whom also received targeted therapy during that yr. Lung cancer dx occurred 1958-2016. Platinum drugs, taxanes, and etoposide were the most common chemotherapies. 46% of chemo recipients (mean age 47, SD 2, range 41-49) experienced immediate menopause, 9% (mean age 43 yrs, SD 5, range 35-48) experienced menopause at least 2 yrs after the age of dx, and 45% (mean age 40 yrs, SD 5, range 25-48) remained pre- or peri-menopausal at their final survey (on average 3 years after dx, SD 2, range 1-10). Only 3 patients received targeted therapy alone, and the remaining 94 (mean age 42 yrs, SD 6 years) received no systemic therapy within a year of diagnosis. 15% of these 94 (mean age 45 yrs, SD 3, range 41-49) experienced immediate menopause, 16% (mean age 43 yrs, SD 4, range 36-49) experienced menopause 2+ yrs after the age of diagnosis, and 69% (mean age 41 yrs, SD 7, range 20-49) remained pre- or perimenopausal at their final survey (on average 4 yrs after dx, SD 3, range 1-10). Conclusions: Chemotherapy for lung cancer causes amenorrhea in a substantial proportion of women dx’d with lung cancer while premenopausal. Further research on fertility and menopausal symptoms after lung cancer treatment, and on differences between regimens, is warranted.

6531 Background: Annual mammography is recommended to screen residual breast tissue for new cancers and recurrent disease after treatment for early stage breast cancer. This study aimed to assess mammography rates over time in breast cancer survivors. Methods: We used administrative claims data from a large U.S. commercial insurance database, OptumLabs, to retrospectively identify privately- and Medicare Advantage-insured women with operable breast cancer who had residual breast tissue after definitive breast surgery between 2006 and 2015. We required coverage for at least 13 months following surgery. For each subsequent 13-month time period, we only included women without a loss of coverage, bilateral mastectomy, metastatic breast cancer diagnosis, or non-breast cancer diagnosis. We calculated the proportion of patients who had a mammogram during each 13-month period following breast surgery. We used multivariable logistic regression to test for factors associated with mammography in the first 13 months. Results: The cohort included 26,011 women followed for a median of 2.9 years (IQR 1.9-4.6) after surgery; 63.1% were less than 65 years of age, and 74.4% were white. In their first year of follow-up, 86% underwent mammography, but by year 7, this decreased to 73%. Fewer than 1% underwent MRI instead of mammography. In multivariable analysis, mammograms were less likely during the first year after surgery among women aged < 50 years (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.6 to 0.8), African Americans (OR, 0.7; 95% CI, 0.7 to 0.8), patients who underwent mastectomy (OR, 0.7; 95% CI, 0.6 to 0.7), and patients residing in the Western part of the country (OR, 0.9; 95% CI, 0.7 to 0.9). Those with 1-2 comorbidities were more likely (OR, 1.1; 95% CI 1.1-1.2) than those with none to have a mammogram during that period. Mammography use did not differ significantly by year of diagnosis (2006-2015). Conclusions: Even in an insured cohort, a substantial proportion of breast cancer survivors do not undergo annual surveillance mammography. Mammography use falls as the time from the early stage breast cancer diagnosis increases. Understanding factors associated with lack of mammographic screening may help improve survivorship care.

6520 Background: Breast cancer follow-up guidelines recommend imaging for distant metastases only in the presence of signs/symptoms. However, data supporting this recommendation predates the current era of improved imaging and targeted therapies based on molecular subtype. The objective was to assess the relationship between mode of distant recurrence detection and survival. Methods: A stage-stratified random sample of Stage II-III breast cancer patients diagnosed in 2006-7 was selected from NCDB records from 1,217 CoC-accredited facilities (10/hospital n = 10,853). Women were categorized by subtype: 1) ER or PR+/HER2-; 2) ER and PR-/Her2- (triple negative); 3) HER2+. Medical records abstracted for 5-years post-surgery supplemented NCDB data and assessed distant recurrence and mode of detection (prompted by signs/symptoms or surveillance imaging), imaging (chest CT, abdomen/pelvis CT/MRI, head CT/MRI, bone scan, PET/CT), death date. The relationship between mode of recurrence detection and days from initial cancer diagnosis to death was assessed using propensity-weighted multivariable Cox proportional hazards regression stratified by subtype. Propensity weights, based on receipt of surveillance systemic imaging, accounted for sociodemographic and tumor/treatment factors. Results: 5-year distant recurrence was 22.3% for triple negative, 14.8% HER2+, and 11.2% for ER or PR+/ HER2- patients. Asymptomatic imaging detected recurrence in 22.9% and signs/symptoms in 77.1%. Patients with asymptomatic as compared to sign/symptom detected recurrences had reduced risk of death in 5 years if triple negative (HR = 0.68, 95% CI = 0.50-0.93) or HER2+ (HR = 0.40, 95% CI = 0.24-0.65) with no significant association for ER or PR+/HER2- (HR = 1.2, 95% CI = 0.88-1.51). This translated to a between-group difference in weighted median survival of 5 months for triple negative and 13 months for HER2+ patients. Conclusions: This is the first nationally representative study to show a survival advantage with asymptomatic detection of distant metastases for patients, with the benefit limited to triple negative and HER2+ disease. Further research to confirm observational findings is warranted.

e12522 Background: Trastuzumab is widely used in management of HER2+ breast cancer patients. A known adverse effect of trastuzumab use is cardiac dysfunction, which can often be reversed with cessation of therapy. Our objectives were to 1) assess if trastuzumab can be safely administered to breast cancer patients with reduced cardiac function and 2) identify patient characteristics that predict susceptibility to trastuzumab-induced cardiac dysfunction. Methods: A retrospective analysis was performed on female patients seen at Mayo Clinic for HER2+ breast cancer and treated with trastuzumab for localized or metastatic disease between January 1, 2000 and August 31, 2015. Eligibility criteria included documentation of and results from at least one echocardiogram prior to and at least one after trastuzumab initiation. Left ventricular (LV) ejection fraction (EF) of 53% or more was considered normal. Any LVEF reduction of 10% or more was considered significant. Among patients with normal EF, age strata of < 45, 45-60, and > 60 at time of trastuzumab initiation were used to assess risk factors for clinically diagnosed cardiac dysfunction (defined as EF < 53 or abnormal strain and physical symptoms of heart failure (HF)). Results: We identified 335 women (mean age 53.3, with 25.3% age < 45, 44.5% age 45-60, and 30.1% age > 60) who had normal LVEF (median EF 64, range: 53-75) and 23 women (mean age 53.4, with 30.4% age < 45, 43.5% age 45-60, and 26.1% age > 60) who had low LVEF at baseline (median EF 52, range: 25-52). Approximately a third (34.3%) of women with normal LVEF prior to initiation of therapy had at least one subsequent echocardiogram showing a drop of 10% or a low LVEF ( < 53). Approximately a quarter (26%) of women with low LVEF at baseline had a 10% drop in LVEF. HF incidence increased with age. Predictive factors for trastuzumab-induced cardiac dysfunction were obesity and history of coronary artery disease (CAD) across all age strata, and chest irradiation (IR) for those aged 45-60 only. Conclusions: Our results suggest that trastuzumab can be administered in women with reduced cardiac function at no greater risk than in those with preserved cardiac function. Some women with no obesity, history of CAD, or history of chest IR may not need echocardiograms during trastuzumab therapy.

531 Background: The greatest age disparity in early stage breast cancer (BC) outcomes is in young women with hormone receptor positive (HR+) BC. While differences in biology may play a role, understanding the role of non-persistence (early discontinuation) with endocrine therapy (ET) is critical given the demonstrated efficacy of ET in this population. Methods: As part of a prospective cohort that enrolled women with BC diagnosed (dx) at age ≤40 between 2006-2016, we identified women with HR+, Stage I-III BC. Socio-demographic and treatment information, fertility concerns and confidence with the ET treatment decision were assessed by survey within 1 yr of dx. Medical record review was used to ascertain stage and HR status. Women who initiated ET but did not report taking tamoxifen or an aromatase inhibitor at 3 yrs post-diagnosis (or last follow-up if <3 yrs) were classified as non-persistent. Chi-square tests were used to compare categorical variables between persisters and non-persisters and stepwise multivariable regression to evaluate predictors of non-persistence. Results: In 538 women who initiated ET, median age at dx was 36; 10% were non-persistent. Discontinuation of ET was more likely in those who were less confident with their ET decision compared to those who were more confident (25/179, 14% vs 18/263, 7%, p=0.01). A greater proportion of women concerned about fertility discontinued vs. women not concerned (29/213,14% vs 25/319, 8%, p=0.03), and fertility concerns were associated with non-persistence in multi-variable analyses (OR: 1.85, 95% CI 1.05-3.26, p=0.03). Age at dx, race, education, employment, financial comfort, marital status, parity, stage, chemotherapy and local therapy were not associated with non-persistence. Conclusions: A significant minority of women with HR+ BC discontinued ET within 3 yrs. The association between fertility concerns expressed soon after dx and non-persistence underscores a need to address psychosocial issues that can impact treatment decisions in young women. Strategies to reduce decisional conflict and increasing confidence with the choice to take ET, may influence persistence. Future work will evaluate the contribution of other factors (eg symptom burden) to non-persistence.

526 Background: Young age at diagnosis (dx) is a predictor of worse prognosis in patients (pts) with luminal breast cancer (BC). Poorer adherence to endocrine therapy (ET) among younger women may contribute to this disparity. Aim: To assess non-adherent behaviors and associated factors among young women with stage 1-3 hormone receptor (HR)+ BC taking ET. Methods: This study is a part of a multi-center, prospective cohort of pts with dx of BC at or under age 40. On a survey 30 months after dx, among pts reporting taking ET, adherence was measured using a 3-item Likert-type scale (Do you ever forget to take your ET? If you feel worse when you take your ET, do you stop taking it? Did you take your ET exactly as directed by your doctor?). Pts reporting any non-adherent behavior during the last 3 months were classified as non-adherers. Variables with a p-value <0.20 were included in a multivariate logistic model. Results: Among361 pts eligible for this analysis, 174 (48%) reported some non-adherent behaviors in the last 3 months; 56 (16%) moderate or greater non-adherent behaviors. None of the studied variables was associated with non-adherent behaviors (table). Conclusions: Non-adherent behaviors to ET are present in almost half of the young women with HR+ BC. Further analyses of explanatory factors and impact of non-adherence are required to understand and potentially improve this problem. [Table: see text]