H. Stephen Gallager

Adenoid Cystic Carcinoma of the Breast

Twelve cases of pure adenoid cystic carcinoma of the breast were reviewed. Patients ranged in age from 34 to 69 years. Seven carcinomas were in the right breast, and five in the left; five of the 12 were located in the central region of the breast, five in the upper outer quadrant, and the two in the upper inner and lower inner quadrants, respectively. Average diameter of the primary tumors was 2.5 cm (range, 0.7 to 6.0). We graded the tumors according to a system used for adenoid cystic carcinoma of the salivary gland: five tumors were grade I, six were grade II, and one was grade III. An average of 5 years after diagnosis, all patients with grade I tumors were either alive without evidence of disease or had died of unrelated causes. Among the six patients with grade II tumors, one developed a local recurrence 5 years after diagnosis and subsequent pulmonary metastasis, and one died of metastatic adenoid cystic carcinoma 13 years after diagnosis. The one patient with grade III tumor had shown metastases in axillary lymph nodes at mastectomy, and she died of disease 2 years later. These findings suggest that the grading of adenoid cystic carcinoma of the breast may be important in prognosis and treatment selection.

Pathologic types of breast cancer: their prognoses

Mammary epithelium gives rise to a wide variety of histologically diverse carcinomas. Some types are associated with predictable patterns of clinical behavior, and it is important that these be recognized since, in many instances, therapeutic modifications are indicated. Among the kinds of breast carcinoma generally considered to have prognoses more favorable than average are adenoid cystic carcinoma, tubular carcinoma, juvenile secretory carcinoma, and perhaps medullary carcinoma with lymphoid stroma. Some of the prognostically unfavorable carcinomas are carcinoma with sarcomatoid metaplasia and inflammatory carcinoma. In applying this information to individual clinical situations, it is critical that a standard classification be consistently used and that its criteria be strictly observed. The 1981 edition of the classification promulgated by the World Health Organization while not flawless, is recommendable, since it includes both concise verbal definitions and admirably clear photomicrographs. Whatever the system of terminology chosen, it should be one equally acceptable to the pathologist responsible for histologic diagnosis and the physician responsible for treatment, and it should be clearly understood by both of them. These special types of carcinoma constitute only a minority of all breast cancers.

Carcinoma of the breast. The prognostic significance of extranodal extension of axillary disease

A retrospective study to determine the effect of extranodal axillary disease on prognosis in invasive carcinoma of the breast was undertaken in a series of 152 cases. It was found that extranodal disease has an unfavorable effect on prognosis in those patients with three or less involved axillary nodes and no effect on prognosis in those patients with four or more involved axillary nodes. Extranodal axillary disease was found to have no influence on the interval between surgery and initial recurrence nor on the anatomic distribution of the recurrence, local or remote.

Sarcomatoid carcinoma of the breast: An immunohistochemical study of six cases

Six cases of sarcomatoid carcinoma of the breast (SCB) were studied with a panel of anti-bodies directed against epithelial and sarcomatoid components. The monoclonal antibodies (MoAb) AE-1/3, CAM 5.2, and CEA were used to detect epithelial differentiation; polyclonal antibodies against S-100 protein and MoAb against the intermediate filaments desmin and vimentin were used to detect mesenchymal differentiation in the sarcomatoid component. Six cases of invasive duct carcinoma (IDC) and two cases of cystosarcoma phyllodes (CP) were compared to SCB using the same panel of antibodies. In all three groups studied, the epithelial component in the majority of cases stained with anti-cytokeratin antibodies. S-100 protein antibodies stained the epithelial and sarcomatoid components in four cases of SCB; vimentin MoAb stained the epithelium in two cases and the sarcomatoid component in four cases of SCB, while MoAb CEA failed to stain any component of SCB. In contrast, the epithelium in five of six cases of IDC stained with CEA MoAb and only one of six stained for S-100 protein. Possible reasons for the discrepant immunohistochemical staining patterns among SCB, IDC and CP are discussed, in addition to the limitations and pitfalls of immunohistochemistry in diagnostic surgical pathology.

Prognostic factors in stage II endometrial carcinoma

The rarity of Stage II endometrial carcinoma and variable treatment modalities have made the evaluation of prognostic factors difficult. Clinical, surgical, and pathologic characteristics were evaluated in 64 patients treated with whole pelvic irradiation and intracavitary radium followed by hysterectomy at The University of Texas M. D. Anderson Hospital and Tumor Institute from January 1965 to December 1983. Comparison of 5‐year actuarial survival rates revealed the following statistically significant categories: age, grade, depth of myometrial invasion, disease extent at surgery including lymph node metastases, and pelvic cytology. Race, weight, and cell type were not significant prognostic factors. Evaluation of prognostic factors at surgery includes pelvic and para‐aortic lymph node biopsies, omental biopsy, pelvic cytologic washings, and biopsy of any suspicious tissues. Patients with adverse prognostic factors are candidates for trials with adjuvant therapy.

The detection and diagnosis of early occult and minimal breast cancer

Radical mastectomy as originally conceived at the turn of the century consisted of complete removal of the breast tissue, the overlying skin, the pectoral muscles, the intervening lymphatics and the axillary lymph nodes. The aim was logical but initially the results were poor. Only 41% of the 76 patients in Halsteds original series were without disease at the end of 3 years. The principal reason for this was the advanced stage of disease in the patients selected for treatment. By contrast, Gilbertsen, using clinical examination alone, surveyed women 45 years of age or older and found that of 32 patients with breast cancers detected by the screening procedure, 24 had no axillary lymph node involvement. The absolute 5-year survival rate of this group was 96%, which approaches the anticipated survival of comparable women free of breast cancer. Those with positive lymph nodes had an absolute survival rate of 75% at 5 years. Further, of 13 patients observed for 10 years, the survival rate for those without node involvement was 90% and for patients with node involvement was 33%. Patients treated at the Barnes Hospital in St. Louis between 1912 and 1933 were contrasted with similarly treated patients at the Barnes Hospital and the Ellis Fischel Cancer Hospital from 1940 to 1955. A poorer survival rate in the earlier series was related primarily to the greater frequency of advanced and larger tumors. That a significant reduction in breast cancer mortality can be achieved is becoming increasingly apparent. Among survey-detected breast cancers in the study conducted by the Health Insurance Plan of Greater New York, the 6-year mortality was half of that of controls. This reduction is even more impressive when one considers that among these patients were many with full invasive, mass-forming carcinomas at the time of initial screening. A recent report by Wanebo, Huvos and Urban discusses the treatment of prognostically favorable forms of breast cancer by modified radical mastectomy. It is possible to select from among their patients those who fit the definition of minimal breast cancer. In this group the 5-year survival rate was 97% and the 10-year survival rate was 95%. Only 1 patient died of breast cancer in 10 years. In another reported group of 65 patients with intraductal carcinoma only, there were no deaths due to breast cancer in 10 years. Should the NCI-ACS demonstration projects show, as now seems probable, that community screening programs can be effective in early breast cnacer detection, it is to be anticipated that widespread public demand for screening facilities will follow. This may present insurmountable logistic and economic problems. The total number of radiologists in the United States is not sufficient to screen annually the total population of women over age 40, or even over age 50. There is great need for the development of criteria for the ready identification of that segment of the population in which most of the cancers would be found...

Pathogenesis of Early Breast Cancer

In 1961, Dr. John Martin and I undertook a collaborative histopathological and radiologic study of breast cancer. We were stimulated to this by the then current upsurge of interest in mammography. We hoped by our study to clarify the relationships between mammographic and histopathological findings in breast cancer. To this end we adopted a subserial whole-organ section technique, a modification of that used by Cheatle many years earlier. Women suspected of having breast cancer were routinely submitted to preoperative mammography. Diagnoses of carcinoma were established by trephine-needle biopsy only, thus leaving tumors essentially intact within the breasts. Each mastectomy specimen was first examined grossly, and the axillary lymph nodes were removed and processed in the usual manner. The breast itself was divided into three large vertical blocks. Each of these was fixed, processed, and embedded in paraffin. Giant sections 12–15 µm thick were cut at 1-mm intervals through each block. Thus, each breast yielded a set of 80–200 large sections that could be arranged in order to provide a three-dimensional representation of the breast. Lesions could be directly compared with mammographic images and point-for-point correlations established.

TREATMENT OF CLEAR CELL ADENOCARCINOMA IN YOUNG FEMALES

Eight cases of clear cell adenocarcinoma treated at The M. D. Anderson Hospital are reviewed. Six such lesions were primarily vaginal carcinomas and 2 involved the cervix. Five patients with early carcinomas were treated entirely with a transvaginal cone or interstitial irradiation and 4 are living and well, 2 to 8 years after completion of therapy. We believe that this experience justifies further treatment of early clear cell carcinomas with conservative radiation. This form of therapy is particularly important since the DES-exposed patients represent an identifiable high-risk group which should augment the chances for early diagnosis.

Minimal Breast Cancer: A Concept and Its Implications

Mammography, followed by biopsy when indicated by certain subtle signs on the mammogram, can identify breast cancer at the “minimal” stage when, in addition to being clinically undetectable, it possesses certain distinctive histopathologic features. Applied to high-risk women, this approach (in combination with existing methods of treatment) can raise the present “early diagnosis” five-year survival rate, to 90% or more.