Pathology and behavior of small breast carcinomas

Mammographic screening and increased public awareness have changed the clinical spectrum of breast carcinoma with important implications for therapy. Small invasive breast carcinomas T1a,b, defined as 1.0 cm or less in maximum diameter, now comprise 22% of invasive carcinomas in our institution, enabling comparison of 273 T1a,b with 563 T1c (1.1 to 2.0 cm), 447 T2 (2.1 to 5.0 cm), and 40 T3 (>5 cm) carcinomas. Nuclear measurements were made with calibrated ocular grids. Hormone receptors were measured in cytosol or immunohistochemically. S-phase fraction (SPF) was measured prospectively on all carcinomas by counting cells in histologic preparations after vitro labeling with tritiated thymidine or 5-bromo-2'deoxyuridine. T1a (0.2 to 0.5 cm) carcinomas were similar to T1b (0.6 to 1.0 cm) in histologic and biologic features, but T1b carcinomas had higher detection rates of axillary metastasis (0% v 10%). The latter may reflect longer duration of metastases, permitting growth to detectable size. Low-grade carcinoma types (mucinous, tubular, cribriform) became less frequent as T stage increased, with the major decrease occurring at T1b (0.6 to 1.0 cm)/T1c (1.1 to 2.0 cm) boundary. T1a,b carcinomas preponderantly had low-grade histologic and biochemical characteristics and low SPF. SPF increased significantly with increasing tumor size from T1b through T2 but not beyond T2. Increases in proportion of patients with axillary metastases occurred over each T transition. Estrogen and progesterone receptor (ER, PgR) positivity decreased with increasing stage. Larger tumors were significantly associated with younger patient age. While this may reflect ease of diagnosing small carcinomas after the menopause, young age was also associated with predictors of aggressive tumor behavior (high SPF, negative assays for ER, PgR). T1a,b patients with mid or high SPF or axillary metastases were more likely than others to have received cytotoxic adjuvant therapy. Conclusions are: (1) Development of cell lines that have metastatic capability appears to occur near the T1b/T1c interface, but they exist very early in some carcinomas. (2) T1a carcinomas may be managed without axillary dissection. When T1b patients are candidates for adjuvant therapy, we advocate sentinel node biopsy with intensive study for micrometastases. (3) Accurate determination of size is very important in prognosis of small breast carcinomas. (4) Prognostic efficacy of proliferation and other prognostic markers in retrospective studies, but not in our patients who often received adjuvant therapy, suggest that micrometastases from small breast carcinomas are highly responsive to adjuvant chemo/hormonal therapy.