Anne M. Wallace

Background: Patients with estrogen receptor (ER)-positive ductal carcinoma in situ (DCIS) derive a greater benefit from endocrine therapy than patients with ER-negative disease. The relevance of ER status and progesterone receptor (PR) status in DCIS to radiation therapy has not been well explored. Methods: Patients undergoing breast-conserving surgery with or without radiation were grouped by ER and PR status and matched using rank-based Mahalanobis optimal matching with respect to lesion size and grade and patient age and race. Cumulative incidences were estimated and competing risk regressions with subdistribution hazard ratios (sHRs) were calculated. Results: Among patients who underwent breast-conserving surgery only, 369 patients with ER-PR- disease were matched to 738 patients with ER+PR+ disease (1:2 matching). In multivariate models, patients with ER-PR- disease were at increased risk of any invasive events (sHR = 2.47, p = 0.007) and early ipsilateral invasive events (sHR = 2.64, p = 0.02 in the 0-to-4-year period) relative to patients with ER+PR+ disease. Among patients who underwent breast-conserving surgery with adjuvant radiation, 1498 patients with ER+PR+ disease were matched to 1498 patients with ER-PR- disease. No significant differences were noted with respect to cumulative incidence of any invasive event (5.6% vs. 5.6%) or ipsilateral invasive events (1.9% vs. 2.9%). In multivariate models, no significant differences were noted. Patients with ER-PR+ lesions had similar cumulative incidences of ipsilateral invasive events to patients with ER-PR- disease in the absence of radiation (5.9% vs. 5.9%) and similar cumulative incidences of contralateral invasive events to patients with ER+PR+ disease when radiation was administered (3.2% vs. 4.2%). Conclusion: The statuses of ER and PR carry independent prognostic and therapeutic implications beyond those of traditional clinicopathologic risk factors. Given that ER and PR statuses are routinely collected for patients with DCIS, incorporation of these variables into clinicopathologic risk classification systems is warranted.

Background/Objectives: Patients with a diagnosis of ductal carcinoma in situ (DCIS) were poorly represented in the four trials that established the efficacy of partial relative to whole-breast irradiation. In contrast to invasive cancers, patients with DCIS are equally likely to have a subsequent ipsilateral invasive event in a different site of the breast from their initial DCIS lesion as they are at the same site. We aim to compare the efficacy of a type of partial-breast irradiation, brachytherapy, to external-beam radiation in the reduction of subsequent invasive cancers. Methods: Women diagnosed with a first breast cancer of unilateral DCIS treated with breast-conserving surgery without endocrine therapy were identified in SEER. Matching was performed 1:2 from patients receiving brachytherapy to patients receiving external-beam radiation or no radiation. External-beam radiation was assumed to be whole-breast radiation for the majority of patients in this cohort diagnosed from 2007 to 2011. Competing risks methods were used to estimate the cumulative incidence of invasive breast events at 10 years and subdistribution hazard ratios (sHRs) in adjusted models with time-varying treatment coefficients were calculated. Results: Among the 1392 matched patients who received brachytherapy or no radiation, the 10-year cumulative incidence of ipsilateral invasive cancer was 5.5% without radiation and 5.7% with brachytherapy (p = 0.92). Brachytherapy was associated with reduced risk of ipsilateral invasive events in the first 3 years (sHR = 0.19, p = 0.03) and non-significantly increased risk after 3 years (sHR = 1.66, p = 0.07). Among the 1392 matched patients who received brachytherapy or external-beam radiation, the 10-year cumulative incidence of ipsilateral invasive cancer was 5.7% with brachytherapy and 3.1% with external-beam radiation. In multivariate regression, brachytherapy was associated with unchanged risk in the first 3 years but increased risk after 3 years (sHR = 2.20, p = 0.009). Conclusions: Our results suggest that brachytherapy may be associated with a higher invasive recurrence risk for patients with DCIS treated without endocrine therapy, as it did not prevent more invasive ipsilateral events than no radiation, and provided reduced risk reduction in the ipsilateral breast relative to external-beam radiation. Further work is needed to identify if this is specific to brachytherapy or applies to all forms of partial-breast irradiation.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.

Trebananib vs Control pCR–Biomarker Associations

RPPA endpoints and genes/signatures involved in TIE2 signaling that were studied

Representativeness of Study Participants

RPPA endpoints and genes/signatures involved in TIE2 signaling that were studied

Trebananib vs Control pCR–Biomarker Associations

Using Contemporary Controls and Adjusting for Time Trends in I-SPY2: The Time Machine