Purpose: Atypical hyperplasia (AH) (ductal or lobular) represents a marker for an increased risk for subsequent breast cancer in either breast, especially in premenopausal women and those with a positive family history. However, the impact of the presence of AH in association with an invasive breast cancer on ipsilateral breast recurrence rates or contralateral breast cancer in women treated with conservative surgery and radiation is unknown. For a number of clinicians the presence of marked proliferative changes with atypia at the time of diagnosis of an invasive cancer is an indication for mastectomy. In an attempt to address this issue, we compared the outcome of patients (pts) with proliferative disease with atypia to those in whom this pathologic feature was absent.Materials and Methods: From 1982-1994, 1537 women with stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. 459 of these women had pathologic evaluation of the background adjacent benign breast tissue and represent the study population. The median followup was 6.3 yrs (range .1-14.5). The median age was 55 yrs (range 24 to 88). 23% had positive axillary nodes. 25% received adjuvant chemotherapy (CMF or CAF) with (9%) or without (16%) tamoxifen. 24% received tamoxifen alone. The study population was divided into 2 groups: 131 pts with atypical hyperplasia (ductal 99 pts, lobular 20 pts, and type not specified 12 pts) and 328 pts with no proliferative changes or proliferative changes without atypia. The comparability of the 2 groups was assessed for the following factors: clinical (race, age, menopausal status, method of detection of primary, primary tumor size, and family history), pathologic (histology, final resection margin, pathologic nodal status, presence or absence of LCIS, histologic subtype DCIS when present and estrogen and progesterone receptor status) and treatment related (re-excision and adjuvant chemotherapy and/or tamoxifen). Outcome was evaluated for ipsilateral breast recurrence, contralateral breast cancer, overall, and cause-specific survival.Results: A statistically significant difference was observed between the 2 groups for method of detection, primary tumor size, the presence of LCIS, pathologic nodal status, and adjuvant therapy. Pts with AH were more likely to have primary invasive cancers ≤2 cm (T1 80% vs 70%) detected solely by mammography (51% vs 36%) and with negative axillary nodes (87% vs 73%). LCIS was observed in 9% of pts with AH and 3% of the pts without AH. Pts with AH were least likely to receive chemotherapy (15% vs 29%), however, 32% received tamoxifen alone compared to 21% of the pts without AH. There were no statistically significant differences between the 2 groups for race, age, menopausal status, family history, histology, histologic subtype DCIS, final margin status, estrogen and progesterone receptor status, or the use of reexcision. 56% of both groups had invasive ductal carcinomas with associated DCIS. In both groups, 63% of the DCIS was classified as non-comedo. The 5 and (10) yr actuarial results are as follows: There were no significant differences in the interval to ipsilateral breast recurrence (4 yrs vs 4.3 yrs) between the 2 groups. However, 1 of the 3 recurrences in pts with AH was in a separate quadrant (20% without AH elsewhere) and was DCIS only (12% without AH DCIS only). The interval to contralateral breast cancer was shorter in pts with AH (1.5 yrs vs 5 yrs).Conclusion: AH does not result in an increased risk of ipsilateral breast recurrence in patients with invasive cancer treated with conservative surgery and radiation. In particular, no increased risk was observed in premenopausal women or those with a positive family history. Based on these results, the presence of proliferative changes with atypia in background benign breast tissue should not be a contraindication to breast conservation therapy for early stage invasive cancer..