Background: Women diagnosed with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and borderline ADH/DCIS are at increased risk for breast cancer, but the precise degree of risk varies widely in the literature. Information from prior studies is limited by grouping ADH and ALH together and by small cohort sizes. Objectives: To identify women with a pathologic diagnosis of ADH, ALH, LCIS, and borderline ADH/DCIS using Natural Language Processing. To evaluate breast cancer risk based on atypia type. Methods: Using Natural Language Processing, we reviewed all electronically available pathology reports from Massachusetts General Hospital, Brigham and Women's Hospital, and Newton-Wellesley Hospital (members of Partners HealthCare System) from 1987–2010. We identified all women with a diagnosis of ADH, ALH, LCIS, and borderline ADH/DCIS with no prior or concurrent diagnosis of breast cancer. We determined the incidence of subsequent invasive and noninvasive breast cancer, the side of cancer diagnosis compared to original atypia side, and the time to cancer diagnosis for each atypia type. Results: We reviewed 76,333 path reports in 42,950 unique individuals and identified 3049 women who were diagnosed with atypical breast lesions over this 14-year period; 1233 (40.4%) had ADH, 851 (27.9%) had ALH, 595 (19.5%) had LCIS, and 370 (12.1%) had borderline ADH/DCIS. The mean age for atypia diagnosis was 51 years (range: 18–93). At a mean follow-up of 66 months, cancer occurred in 7.0% of women with ADH, 11.3% of women with ALH, 11.1% of women with LCIS, and 8.4% of women with borderline ADH/DCIS. The median time to breast cancer diagnosis was 48 months with ADH, 50 months with ALH, 47 months with LCIS, and 60 months with borderline ADH/DCIS. Significantly more ipsilateral cancers developed than contralateral cancers for all types of atypia combined (p=0.027). The development of invasive versus noninvasive breast cancer was not significantly affected by atypia type. Subsequent cancers were DCIS in 121 patients (43.4%) and invasive in 158 patients (56.6%). Kaplan Meier curves for time to cancer diagnosis based on atypia type were created. The curves for ADH and borderline ADH/DCIS were similar and significantly different than the curves for ALH and LCIS (p<0.001). The estimated 5 and 10-year breast cancer risks for each atypia type are presented in Table 1. Conclusion: A diagnosis of ADH, ALH, LCIS, or borderline ADH/DCIS increases a woman's risk of invasive and noninvasive breast cancer in either breast. The breast cancer risk at 5 and 10 years is significantly higher in those with ALH or LCIS compared to those with ADH or borderline ADH/DCIS, but there is little difference in risk between ADH and borderline ADH/DCIS or between LCIS and ALH. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S4-4.
Introduction: Non-classic lobular carcinoma in situ (NC-LCIS) is a rare pathologic entity which encompasses a variety of histologic diagnoses. As such its natural history, including upgrade rates to invasive cancer (IC) or ductal carcinoma in situ (DCIS) on excision, is poorly characterized. We sought to evaluate the risk of upgrade to IC or DCIS when NC-LCIS is diagnosed on core biopsy. Methods: After obtaining IRB approval, institutional pathology databases were searched for NC-LCIS core biopsy diagnoses (carcinoma in situ (CIS), carcinoma in situ with ductal and lobular features (CIS/DLF), pleomorphic LCIS (P-LCIS), variant LCIS (V-LCIS), LCIS with necrosis). Cases with a NC-LCIS core biopsy diagnosis and with available pathology results from subsequent surgery were included. Cases with known concurrent ipsilateral IC, DCIS and/or atypical ductal hyperplasia were excluded. Results: 107 cases with NC-LCIS in any pathology report were identified (1998-2016); 44 were excluded due to concurrent ipsilateral IC, the remaining 62 patients with 63 core biopsy diagnoses of NC-LCIS all underwent surgical excision and formed our study cohort. Median age was 56 years (range 43-83); 43 (68%) were postmenopausal. NC-LCIS was diagnosed on core biopsy for mammographic findings in 57 (90%) cases and for MRI findings in 6 (9%). All were BI-RADS 4 lesions; calcifications were the most common biopsy indication (50 (78%)). CIS/DLF was the most common term used for NC-LCIS (28 (44%)), followed by CIS (18 (29%)), V-LCIS (14 (22%)) and P-LCIS (3 (5%)). On core biopsy, 36/44 (82%) of NC-LCIS cases were E-cadherin negative, 38/41 (93%) were ER positive, and 6/34 (18%) were HER2 positive. IC and/or DCIS were diagnosed on subsequent surgery in 22 (33%) of patients, of which 14 (67%) were IC and 8 (18%) had DCIS only. LesionTotalE-cadherin negativeUpgraded, N (%)Invasive cancer, N (%)DCIS only, N (%)CIS188/10 (80%)3 (16%)2 (67%)1 (33%)CIS/DLF2819/23 (83%)12 (43%)7 (58%)5 (42%)P-LCIS31/1 (100%)3 (100%)2 (67%)1 (33%)V-LCIS148/10 (80%)4 (29%)3 (75%)1 (25%) Median IC size was 0.2 cm (0.06-1.1 cm). IC histology was ductal in n=4 (29%), lobular in n=7 (50%), and ductal and lobular in n=3 (21%). Among the 14 invasive lesions, 5 (36%) were grade I, 5 (36%) were grade II and 2(13%) were grade III, (grade was not reported for 2 remaining ICs); 12/14 (86%) were ER positive and 1/14 (7%) was HER2 positive; none had LVI or positive nodes. Among the 42 cases not upgraded, 13 (31%) had mastectomy, 9 (21%) had excision and radiation, 20 had excision only, all had negative margins. At median follow-up of 60 months (1-224 months), 1/20 patients treated with excision only was diagnosed with DCIS, 14 months after surgery for CIS/DLF on core biopsy. Conclusions: In this large series of NC-LCIS diagnosed on core biopsy, the upgrade rate to carcinoma was 33% supporting the recommendation for routine excision of these lesions. The cancers found at excision were all stage I and the majority were grade I or II. At a median follow-up of 60 months only 1/20 patients with pure NC-LCIS treated with excision alone developed a future ipsilateral cancer. Further study of the natural history of these rare lesions is warranted. Citation Format: Nakhlis F, Harrison BT, Lester SC, Hughes KS, Coopey SB, King TA. Evaluating the risk of upgrade to invasive breast cancer and/or DCIS on excision following a diagnosis of non-classic lobular carcinoma in situ [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 P5-22-01.
Background: The addition of pertuzumab to trastuzumab and chemotherapy significantly improves the pathologic complete response (pCR) rate in HER2+ localized breast cancer in the preoperative setting. Although many patients are converted to breast conserving therapy (BCT) candidates by neoadjuvant HER2-directed therapy, a significant proportion opt for a mastectomy for various reasons. Among mastectomy procedures, nipple sparing mastectomy (NSM) is frequently chosen instead of non-nipple sparing mastectomy (NNSM). In this study, we evaluated the surgical and long-term outcomes of HER2+ patients receiving neoadjuvant pertuzumab-containing regimens. Methods: We performed a retrospective review of localized breast cancer patients treated with neoadjuvant pertuzumab-containing regimens from 2011 to 2016, who underwent BCT or mastectomy at an academic institution and two community-based practices. Disease characteristics, treatment regimens, surgical outcomes, and recurrence data were extracted from the electronic medical records. Results: Among 90 patients with stage II-III HER2+ breast cancer, 45 received AC-THP (50.0%), 26 received THP (with adjuvant AC) (29.0%), and 19 received TCHP (21.0%). The majority of patients had grade 3 tumors (61.1%), clinical stage II disease (80.0%), invasive ductal carcinoma (86.7%), and ER+ disease (65.6%). Thirty-seven (41.0%) patients underwent BCT and 53 (59.0%) patients underwent mastectomy. Among the mastectomy patients, 38 (71.7%) patients underwent bilateral mastectomies, specifically 33 (62.0%) patients underwent a NSM and 20 (38.0%) patients underwent a NNSM. The type of surgery that patients underwent stratified by type of neoadjuvant regimen is outlined in the Table 1 below. Most patients who underwent BCT and mastectomy received radiation, including 36 (97.3%) BCT, 24 (72.7%) NSM, and 18 (95.0%) NNSM. Over a median follow-up period of 33 months, 6 patients (6.7%) had recurrences with 2 (2.2%) local recurrences and 4 (4.4%) distant recurrences. The 2 local recurrences occurred in one patient who underwent BCT and one patient who underwent NNSM followed by post-mastectomy radiation. Conclusions: Among mastectomy patients, NSM was more commonly pursued than NNSM. Rates of local recurrence following pertuzumab-containing regimens for HER2-positive localized breast cancer were low overall, regardless of the type of surgery. Data on plastic surgery approaches and complication rates will be presented at the meeting. Table 1.Type of surgery in patients receiving neoadjuvant HER2-directed therapy. AC-THP (N = 45)TCHP (N = 19)THP (N = 26)BCT46.7%47.4%26.9%NNSM26.7%10.5%23.1%NSM26.7%42.1%50.0% Citation Format: Haddad SA, Spring LM, Jimenez RB, Vidula N, Comander A, Shin JA, Coopey SB, Gadd MA, Hughes KS, Taghian A, Smith BL, Isakoff SJ, Moy B, Bardia A, Specht MC. Surgical and long-term outcomes of patients receiving neoadjuvant pertuzumab-containing regimens for HER2-positive localized 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 P2-14-19.
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