Elsevier

The Lancet

Volume 361, Issue 9352, 11 January 2003, Pages 125-129
The Lancet

Articles
Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study

https://doi.org/10.1016/S0140-6736(03)12230-1Get rights and content

Summary

Background

Clinical decisions about atypical lobular hyperplasia are based on the belief that later invasive breast-cancer risk is equal in both breasts. We aimed to show laterality and subsequent risk implications of invasive breast cancer in women with atypical lobular hyperplasia.

Methods

We did a retrospective cohort study of 252 women who had undergone 261 benign surgical biopsies that showed atypical lobular hyperplasia from 1950 to 1985, as part of the Nashville Breast Studies. Primary outcomes were development of invasive breast cancer and laterality of cancer compared with side of the biopsied breast.

Findings

50 (20%) of 252 women treated by biopsy only developed invasive breast cancer. Relative risk of breast cancer in women with atypical lobular hyperplasia was 3·1 (95% CI 2·3–4·3, p<0·0001). Of these 50 women, the breast with invasive cancer was the same breast diagnosed with atypical lobular hyperplasia (ipsilateral) in 34 (68%) and the contralateral breast in 12 (24%). The ratio of ipsilateral/ contralateral cancers for atypical lobular hyperplasia without other atypical lesions was 17/5. For six women with atypical lobular hyperplasia plus atypical ductal hyperplasia, the ratio was 1/1.

Interpretation

Invasive carcinoma after atypical lobular hyperplasia is about three times more likely to arise in the breast diagnosed with atypical lobular hyperplasia than in the opposite breast without these initial findings. Our findings suggest a model of premalignancy for atypical lobular hyperplasia intermediate between a local precursor and a generalised risk for both breasts.

Introduction

Lobular neoplastic breast disease in women has been judged a special type of premalignancy since the 1940s.1 During the 20–30 years after the description of lobular carcinoma in situ, the term lobular neoplasia was used to describe a range of lobulocentric distortion by characteristic cells, from striking (lobular carcinoma in situ)1 to minimum (minimally atypical lobular hyperplasia).2 Atypical lobular hyperplasia is the diagnostic term most frequently used3, 4, 5 to denote most lobular neoplasia lesions. The cancer-risk implications of atypical lobular hyperplasia have been verified in formal follow-up studies.6, 7, 8, 9

There has been increasing recognition that risk implications for the various components of lobular neoplasia (atypical lobular hyperplasia vs ductal involvement with cells of atypical lobular hyperplasia vs lobular carcinoma in situ) vary with the amount of histological evidence.1, 8, 10 Risk of breast cancer after atypical lobular hyperplasia can also vary with respect to menopausal status.6 We aimed to update results of our previous follow-up studies of lobular neoplasia (mainly including patients with atypical lobular hyperplasia, but also those with ductal involvement with cells of atypical lobular hyperplasia, minimally atypical lobular hyperplasia, and lobular carcinoma in situ),1, 2, 8, 11 and we included additional women identified with atypical lobular hyperplasia in benign breast biopsy samples in Nashville, TN, USA, for 1969–85.

The subsequent risk of invasive breast cancer after the finding of non-invasive lobular neoplasia at time of biopsy has been shown by results of early studies done at Memorial Hospital, New York.12, 13, 14 Researchers widely believe that cancer risk is evenly distributed between both breasts. However, review of published work during this period shows that the risk in some series was about two-thirds in the ipsilateral breast and a third in the opposite (contralateral) breast.13, 14 We aimed to document laterality of subsequent invasive breast cancer (ipsilateral vs contralateral) compared with previous biopsy findings in women with atypical lobular hyperplasia. Results of two major follow-up studies of women with a history of atypical lobular hyperplasia have shown a predominance of subsequent invasive carcinomas in the same breast as biopsy-proven atypical lobular hyperplasia.8, 9 We also aimed to ascertain whether breast-cancer risk after atypical lobular hyperplasia is equal in both breasts.

Section snippets

Participants

We followed up women who were initially enrolled in the Nashville Breast Studies.11 In this large study, procedures were done at three hospitals in Nashville, TN, USA: Vanderbilt University Medical Center, between 1952 and 1985; St Thomas' Hospital, between 1950 and 1983; and Baptist Hospital, between 1952 and 1968. Biopsies were usually done for perceived palpable density in a breast, unrelated to atypical lobular hyperplasia. Data for women with atypical lobular hyperplasia who underwent

Results

During the course of the Nashville Breast Studies,11 we reviewed 17 170 breast biopsy samples taken between 1950 and 1985. A total of 457 (2·7%) biopsies with atypical lobular hyperplasia were identified for inclusion in our study, of which 297 biopsies in 282 women met entry criteria. Most of the 160 ineligible biopsies were done on women with a previous history of cancer or who underwent a bilateral mastectomy on diagnosis.

We obtained follow-up data for 264 (94%) of these 282 women (table 1).

Discussion

In our cohort of 252 women with atypical lobular hyperplasia treated by biopsy only, invasive carcinoma after atypical lobular hyperplasia was about three times more likely to arise in the breast diagnosed with atypical lobular hyperplasia than in the opposite breast.

Since its initial acceptance as a prospective indicator of increased cancer risk, belief in the clinical implications of lobular neoplasia (lobular carcinoma in situ, atypical lobular carcinoma) has been consistent.12, 13, 14 The

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