Abstract

Abstract Introduction LCIS is considered both a risk indicator and a non-obligate precursor of invasive breast cancer. A diagnosis of LCIS confers a risk that is 8-10x higher than that of the general population; yet we remain unable to predict risk of progression and hence lack the tools to make personalized treatment recommendations. Here we examine the relationship between pathologic features and extent of LCIS at surgical excision with risk of subsequent breast cancer. Methods From a prospective database of 1032 patients with LCIS diagnosed from 1980-2009, we identified patients with and without a subsequent cancer diagnosis and created a nested case-control cohort study. A case was defined as a breast cancer diagnosis ≥6 months after LCIS diagnosis. All cases were matched to ≥1 control (cancer free) based on age at diagnosis of LCIS +/- 5 yrs and length of follow up. All H&E slides from the first diagnosis of LCIS were requested for central pathology review. Comparisons between cases and controls were done using conditional logistic regression analysis. Results At median followup of 79 mos (2-368mos) 156 pts (15%) in the parent database have developed breast cancer. Case-control matching resulted in a study cohort of 72 cases and 274 controls for which the original LCIS diagnostic slides were available. There were no significant differences in clinical characteristics between the study cohort and the parent population. Median time to cancer among cases was 3.6 yrs (0.5-12.7yrs). Median cancer-free follow up for controls was 9.9 yrs (1.1-19.8yrs). No significant differences in any of the features examined were observed between cases and controls (Table). Although the median number of slides with LCIS did not differ, the ratio of the total number of slides with LCIS over the total number of slides reviewed was significantly associated with case-control status. Cases had a significantly higher ratio (median 0.5, (0.3-1.0)) than controls (median 0.3, (0-1); p=0.003). On conditional logistic regression analysis, a ratio of >0.5 was associated with a 2.7 (95%CI, 1.4-4.9) greater odds for cancer development when compared to a ratio of <0.25 (p=0.008). Conclusion In this nested case-control study, the quantity of LCIS at excision, as measured by the ratio of the number of slides with LCIS over the total number of slides reviewed, was found to be a significant predictor of subsequent breast cancer. Patients with LCIS in >50% of slides reviewed had a 2.7 increased odds for cancer; suggesting that the extent of LCIS in a biopsy specimen should be considered when counseling patients about future risk and risk reducing options. Table 1 Cases n=72Controls n=274p-valueBilateral LCIS at diagnosis2 (3%)6 (2%)0.81Multicentric LCIS at diagnosis7 (10%)25 (9%)0.68Recurrent LCIS over time9 (13%)24 (9%)0.30Median # slides with LCIS4 (1-19)3 (1-41)0.42Median # TDLU with LCIS11 (1-129)6 (1-342)0.40Cell Type[br]A[br]A/B[br]B24 (33%)[br]45 (63%)[br]3 (4%)99 (36%)[br]145 (53%)[br]30 (11%)0.70Nuclear Grade[br]1[br]2[br]314 (19%)[br]54 (75%)[br]4 (6%)58 (21%)[br]189 (69%)[br]27 (10%)0.54Necrosis06 (2%)NACalcifications27 (38%)114 (42%)0.57Ductal Extension60 (83%)249 (91%)0.09ALH12 (17%)31 (11%)0.19 Citation Format: Jessica C Gooch, Elena Guerini-Rocco, Sujata Patil, Starr B Koslow, Marina De Brot, Anna Y Park, Camilla A Boafo, Jorge S Reis-Filho, Tari A King. The extent of lobular carcinoma in situ (LCIS) at surgical excision predicts for the development of subsequent breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-13-02.

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