William H. Hartmann

Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis

The prognostic significance of histologic tumor grade has been evaluated in 1537 women entered into the Ludwig Trials I‐IV of adjuvant therapy for node‐positive breast cancer. Tumor grade was determined on histologic review of primary tumor sections by two central review pathologists using a modification of the Bloom and Richardson grading system. The 5‐year overall survival rates (±SE) were: Grade 1, 86% ± 2; Grade 2, 70% ± 2; and Grade 3, 57% ± 2 (P <0.0001). This survival difference was seen in both premenopausal (P <0.0001) and postmenopausal (P <0.0001) women. Significant differences in disease‐free survival (DPS) by tumor grade were also observed (P <0.0001). The tumor grade determined by the 75 contributing local clinic pathologists was also highly significant for predicting DPS and overall survival. Tumor grade remained a statistically significant prognostic factor for DPS (P <0.0001) and overall survival (P <0.0001) in multivariate analyses controlling for nodal status, tumor size, estrogen receptor status, menopausal status, age, peritumoral vessel invasion, and treatment assigned. In postmenopausal patients for whom adjuvant treatment was compared with no adjuvant therapy, the prognostic significance of tumor grade was modified by the effect of treatment. The presence of vessel invasion by primary tumor cells was a stronger predictor of early recurrence than was increasing tumor grade in postmenopausal patients who received no adjuvant therapy. The higher failure rates for patients with high‐grade tumors was due to a larger number of failures in regional and visceral sites. Tumor grade can be determined by any pathologist and allows for selection of a subpopulation of breast cancer patients at high risk for early mortality.

Exploration of factors affecting mammography behaviors.

Of an estimated pool of 1,700 potential participants, only 382 (22%) eligible women participated in a low-cost breast cancer screening program offered to university and medical center employees. Because most women were still available and data were needed to understand why the opportunity to participate was refused by so many, a survey was done to determine factors related to mammography behavior. Three distinct groups of women were identified according to health beliefs, mammography behaviors, and modifying factors. Women who participated in the mammogram program were predominantly well-educated working women who were aware of mammography and its relationship to the breast cancer trajectory; they were affected by cost and convenience issues. One group of women did not participate in the program offered because they had had a recent mammogram; these women were at high risk for breast cancer and perceived mammography to be beneficial. The women who did not participate for other reasons were in nonprofessional jobs, had lower levels of education, and tended not to participate in the health care system as readily as women in the other groups; they perceived themselves less susceptible to breast cancer, valued mammography less, and knew less about breast cancer.

Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis

To assess the prognostic significance of peritumoral vessel invasion, data were examined for 1,510 women entered into the Ludwig Breast Cancer Group Trials I to IV evaluating adjuvant therapy for operable breast cancer with axillary nodal metastasis. Vessel invasion by tumor cells was identified by routine light microscopy in 59 per cent (889 of 1,510) of the patients and was equally distributed between premenopausal/perimenopausal (60 per cent, 468 of 778) and postmenopausal (58 per cent, 421 of 732) women. In logrank analyses stratified by nodal status (one to three or four or more positive nodes), the four-year disease-free survival (DFS) rate was significantly lower in patients with vessel invasion than in women without vessel invasion (50 per cent versus 65 per cent, P less than 0.0001). This DFS difference was seen for both premenopausal/perimenopausal (P = 0.0004) and postmenopausal (P = 0.0002) patients. The four-year overall survival rate was also lower in patients with vessel invasion (71 per cent versus 82 per cent, P = 0.0006), both for premenopausal/perimenopausal (P = 0.002) and postmenopausal (P = 0.04) women. The presence of vessel invasion was significantly associated with increasing numbers of positive axillary lymph nodes, rising tumor grade, nonstellate tumor border growth pattern, and higher steroid hormone receptor content of the primary tumor. The assessment of peritumoral vessel invasion continued to have prognostic significance for DFS (P less than 0.0001) and overall survival (P = 0.003) when evaluated in multivariate models controlling for treatment assigned, nodal status, tumor size, estrogen receptor status, menopausal status, and age. Depending on the subpopulation, patients with vessel invasion had a 41 per cent to 54 per cent greater risk of treatment failure than those without vessel invasion and a 29 per cent to 64 per cent greater risk of death. The percentage of treatment failures at distant sites was higher for women with than for those without vessel invasion (27 per cent versus 18 per cent, P = 0.003). In patients with axillary lymph node metastases, peritumoral vessel invasion may be a sign of increased systemic disease burden.

Mastopathy in insulin-dependent diabetics

A type of mastopathy is unique to insulin-dependent diabetic patients. The characteristic change is a connective tissue overgrowth with vasculitis and some proliferation of duct epithelium. It is not the type of change typically associated with an increased risk of breast cancer. Clinically this change is indistinguishable by physical or radiographic findings from breast malignancy. Eleven biopsies showing these characteristics were performed on insulin-dependent patients who had diabetes mellitus from childhood. Every patient had some major complication of diabetes mellitus, usually diabetic retinopathy. In every instance the mastopathy continued to manifest itself as a part of the healing process. The probability is that this is an evidence in the breast of collagen cross-linking changes seen in patients with diabetes mellitus. This observation should help in the supervision of patients with a clinical background compatible with this study.

Receptor heterogeneity of human breast cancer as measured by multiple intratumoral assays of estrogen and progesterone receptor

Multiple intratumoral tissue samples from the primary mass of 30 consecutive invasive breast cancer patients were assayed for estrogen receptor (ER) and progesterone receptor (PR) by the dextran-coated charcoal method following frozen section histopathological examination. Steroid receptor status of each sample was classified as positive (R+) or negative (R-), based only upon quantitative guide lines from the ER/PR results. Four out of 32 (12.5%) of the invasive cancers had an intratumoral sample classified as R+ and one sample as R-. R+ invasive ductal carcinomas has a highly significant degree of tubule formation (P = 0.005) when compared with R- invasive ductal cancers. While the quantitative ER content (r = 0.18) and the degree of quantitative variation in ER content (P = 0.04) did not correlate with the tumor cellularity of the individual samples, tumor cellularity (P = 0.005) and ER content (P = 0.005) were lower in the samples from the tumor border than from the central tumor samples. Variations in ER and PR content may be found on a regional basis within a breast tumor mass resulting from heterogeneity of tumor subpopulations and/or differences in tumor cellularity.

Breast cancer report

The recent increased public awareness of the necessity for early diagnosis of breast cancer has been accentuated by an intense exposure by the news media centering about the disease. This publicity includes the unfortunate but timely clinical sources of the wives of the President and the Vice President of the United States, Mrs. G. F. Ford and Mrs. N. A. Rockefeller. This paper attempts to quantitate in a subjective manner the impact of the events on the American public by comparing the incidence of operative procedures in similar populations in the Nashville community during October through December, 1973, and October through December, 1974, the latter period following the operative procedures upon Mrs. Ford and Mrs. Rockefeller. A statistically significant increase was noted in patients seen, biopsies performed, and cancers detected.

Comparative Pathological Study of Breast Carcinoma among American and Japanese Women

Breast carcinoma among Japanese females is characterized by a relatively low incidence and good prognosis.(6) The recent annual death rate due to breast carcinoma among Japanese females is 5 per 100,000. This death rate is about one sixth of that among American females. According to Cancer Incidence in Five Continents,(2) the annual incidence of breast cancer per 100,000 Japanese females ranged from 12.1 in Osaka Prefecture to 16.6 in Okayama Prefecture. This incidence is very low when compared with that of American females. In Connecticut, the incidence is 71.7 per 100,000 females.