Improved prediction of survival in advanced adenocarcinoma of the ovary by immunocytochemical analysis and the composition adjusted receptor level of the estrogen receptor.

Conventional cytosol estrogen receptor analysis is not a significant prognostic variable in serous ovarian carcinoma. Although the use of immunocytochemical receptor analysis for estrogen does provide prognostically useful information in enhanced accuracy of predicting survival in patients with ovarian cancer, its usefulness can still be improved. Surgical samples from ovarian carcinomas are heterogeneous in tissue composition. Immunocytochemical receptor analysis allows for the specific assessment of the tumorous portions of a histological specimen. However, it is limited by its dependence on staining intensity as the determining factor. Biochemical receptor analysis does provide objective information concerning the number of receptor molecules present in a given sample, but the value is not adjusted for histological composition of the tumor section. Therefore, we have attempted to combine the advantages of both methods. By adjusting the conventional receptor analysis for the percentage of tumor present in the specimen, we have eliminated the tissue heterogeneity as a confounding variable. The resulting value is named Composition Adjusted Receptor Level or CARL. A prospective study was performed on the estrogen receptor concentrations in 61 ovarian cancers. Minimum follow-up was 8 years. For the percentage of tumor in the specimen, a highly significant correlation of the assessment of the two pathologists was observed. Stage (P < 0.05) and grade (P < 0.05) as well as cell type (P < 0.05) were found to be significant prognostic variables. In an attempt to eliminate the confounding influences of these variables, the CARL of the estrogen receptor was assessed with regard to its prognostic significance in 32 grade 2 and 3 serous carcinomas of the ovary, stage III and IV. A linear correlation between CARL and survival was found above a threshold estrogen receptor concentration of 15 fmol/mg cytosol protein using a correlation of the Cox proportional hazards model (P < 0.02). Our data suggest that (a) the assessment of the percentage of tumor in a given sample is not significantly observer dependent, (b) CARL is a significant predictor of survival in serous ovarian carcinoma, and (c) a CARL should be determined for the analysis of any cytosol receptor in solid tumors.

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.

Breast specimen radiography. Obligatory, adjuvant and investigative.

The development of mammography and that of breast specimen radiography, which have paralleled one another, are reviewed. The preparation of radiographs of breast specimens is obligatory when biopsy is performed for purely mammographic indications and when no palpable mass is present. Such cases are being encountered with increasing frequency because of the development of centers for breast cancer screening. Close collaboration among pathologists, radiologists and surgeons and precise attention to procedural detail are necessities wherever this situation arises. The application of specimen radiography as a routine to all breast specimens is regarded as an adjunct to gross examination. While useful, its yield of otherwise undetected occult carcinoma is low. Whether other advantages outweigh the cost appears to be a matter for individual decision. Investigative uses of breast specimen radiography have received little attention. Some possible applications are suggested.

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 DEX-exposed patients represent an identifiable high-risk group which should augment the chances for early diagnosis.

The significance of residual tumor after preoperative pelvic irradiation for stage II endometrial carcinoma.

The prognostic significance of residual endometrial carcinoma in the hysterectomy specimen after preoperative radiotherapy is controversial. Sixty-two patients with stage II endometrial carcinoma were treated with a standardized program of preoperative radiotherapy, followed in six weeks by an extrafascial hysterectomy. Twenty patients (32%) had no residual carcinoma in their hysterectomy specimens and 42 (68%) had residual carcinoma. There were no significant clinical, surgical, or pathologic differences between patients with or without residual carcinoma. Patients with no residual carcinoma had a 25% recurrence rate and a 53% actuarial five-year survival rate. Patients with residual carcinoma had a 21% recurrence rate and a 78% actuarial five-year survival rate. The presence of residual endometrial carcinoma in the hysterectomy specimen does not imply a compromised prognosis in patients with stage II endometrial carcinoma treated by the described method.

Problems in the classification of breast cancer.

This article has sought to clarify the problems that beset the histologic classification of the numerous forms of breast cancer. Not only is classification itself difficult, but our lack of complete understanding of breast cancer often leaves us without criteria sufficiently clear to establish definite categories. Any adopted classification can be expected to require repeated revision as new information becomes available. Uniformly applying a classification will forever be hampered by factors inherent in the practice of surgical pathology and by the nature of breast disease. Considering the inherent problems, there is surprising uniformity among pathologists interested in the study of mammary carcinoma. The diversity is not so much an omen of impending chaos as a manifestation of a continuing struggle to understand the disease better.

Prognosis and treatment in minimal breast cancer.

Of 176 patients with minimal breast cancer, 138 had intraductal carcinoma in situ, 21 minimally invasive carcinoma, and 17 lobular carcinoma in situ. Various modalities of treatment were used including radical, modified radical, and simple mastectomy with and without radiation therapy. Long-term postoperative follow-up was available in all but five patients and ranged from one year to twenty-one years. Actuarial analysis projected a twenty year survival of 93.2 per cent for the entire group. Analysis of survival figures based on each of the several treatment modalities showed no definite advantage of one form of treatment over another. The data suggest that minimal breast cancer is a prognostically favorable diagnosis, provided invasive carcinoma is not present or does not develop in the opposite breast. It is also indicated that breast cancer is potentially a bilateral disease and that follow-up and treatment of the opposite breast must be of major concern in the care of these patients.

The detection and diagnosis of early occult and minimal breast cancer.

This article has attempted to describe the present status of efforts toward routine detection of breast cancer at a stage when it is readily curable and to point out, not only the potentials of screening programs, but also the problems and difficulties that beset them. We believe that efficient, safe screening and accurate early diagnosis are achievable and that trial directed toward this end should not only continue but expand. We see no other avenue that offers as bright a prospect for a meaningful reduction in breast cancer mortality and the monstrous toll--medical, emotional, sociologic and monetary--it exacts.

Correlation of estrogen receptor level and lipid staining in breast carcinoma.

Intracytoplasmic lipid was demonstrated in 10% or more of the cells in 13 (26%) of 50 estrogen receptor (ER)-positive breast carcinomas and in four (14.8%) of 27 ER-negative breast carcinomas. Thus, proportionately more positive tumors contained significant amounts of intracytoplasmic lipid. The difference, however, was not statistically significant. Furthermore, the presence of lipid as a test to predict the ER status is not useful because of its low efficiency and predictive value.

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 Halsted's 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...

The developmental pathology of breast cancer.

The early stages in the development of breast cancer, from epithelial inception to initial invasion, comprise a predictable, fairly uniform series of events. Once invasion has occurred, behavior is much more random. For this reason, local treatment methods are most effective in these early stages and efforts directed at early detection are thoroughly justified.

Prognostic importance of histologic type in ovarian carcinoma.

It is widely accepted that there exists a simple relationship between histologic type and prognosis in ovarian cancer. There are, however, multiple reasons to believe that if there is such a relationship, it is complex and involves many interacting factors. The factors concerned relate both to the biologic natures of the several neoplasms in this group and to the practical limitations to adequate evaluation imposed by clinical circumstances. Many questions remain to be answered before a prospective comparison of various treatment modalities can be expected to produce truly conclusive results.