Jerome A. Urban

Cancers metastatic to the breast

During a period of 10 years, 51 patients were found to have metastatic cancer in the breast. There were 44 women and seven men. Eighteen patients had carcinoma, 16 had malignant lymphoma, 14 had malignant melanoma, and three had myosarcomas. It is interesting that 16 of the 51 patients had no prior history of malignant disease—the mammary lesion presenting as the first manifestation of an occult extramammary primary. Metastatic cancer should be suspected when a multinodular neoplasm is found in the superficial tissues of the breast. Forty‐one patients had a rapidly fulminating course and died of disease. Ten patients are alive, seven with and three without apparent evidence of disease. It is concluded that earlier recognition of these tumors may lead to more rational therapy and avoidance of unnecessary radical surgery.

Residual mammary carcinoma following simulated partial mastectomy.

Treatment of mammary carcinoma by partial mastectomy rather than by total mastectomy and axillary dissection may diminish the chances of long‐term cure by risking incomplete removal of all local carcinoma at the initial operation. This study was undertaken to determine by pathologic examination how often carcinoma might remain in the breast and axilla after partial mastectomy. The operation was simulated in 203 mastectomy specimens after operations for unilateral invasive carcinoma. In so far as could be determined on gross examination, the entire primary lesion was included in the quadrant which was excised in the simulated procedure. Among 100 women with primary lesions less than 2 cm in diameter, 26% had carcinoma in the breast which remained after simulated partial mastectomy. Six percent of them also had axillary node metastases. An additional 30% only had axillary node metastases. When the primary lesion was more than 2 cm in diameter, 38% of patients had carcinoma in the breast after simulated partial mastectomy, of whom 29% also had axillary metastases. After simulated partial mastectomy, carcinoma was found in 80% of breasts from patients with lesions in the subareolar area, in contrast with 25–35% of patients with a primary carcinoma in one of the four quadrants. None of the 9 patients with medullary and colloid carcinomas that measured under 2 cm had axillary metastases or carcinoma in the breast outside of the primary quadrant. The findings suggested that a familial history of breast carcinoma or a large primary lesion may be associated more often with multifocal disease, but factors such as age at diagnosis, axillary status, and the mammogram report did not have significant predictive value for distinguishing between patients who did or did not have carcinoma in breast tissue after the primary had been removed by a simulated partial mastectomy.

Paget's disease of the breast

Two‐hundred and fourteen cases of histologically proven Pagets disease of the breast were seen at Memorial Hospital during the period 1950 through 1968. Ninety‐six patients were without palpable masses, clinically, and 113 had Pagets disease of the nipple with palpable masses. Two thirds of the patients without palpable masses, clinically, had noninfiltrating carcinoma, and the majority of them had negative nodes in the axilla; accordingly, they have a good prognosis. Ninety percent of the patients with palpable masses had infiltrating carcinoma, and two thirds of them had positive nodes in the axilla. According to this study, modified radical mastectomy is the treatment of choice for the patient who does not have a palpable mass. Radical mastectomy should be performed on the patient who has a palpable mass.

Treatment of minimal breast cancer

Modified radical mastectomy was performed in 162 patients with minimal breast cancer between 1953 and 1972 (JAU). The majority of lesions were small infiltrating cancers (52), non‐infiltrating duct cancer (37), lobular carcinoma in situ (49), Pagets disease with non‐infiltrating cancer (12), and also a small group of miscellaneous low‐grade cancers (7), and malignant cystosarcoma phyllodes (5). Major indications for surgery were the presence of a mass, nipple ulceration, positive mammograms, and the discovery of an occult cancer on contralateral biopsy. Mammography was accurate in 60% of patients with minimal breast cancer. Contralateral biopsy proved to be a very sensitive diagnostic technique, and was positive in 35 patients, most of whom were negative by clinical examination and mammography. Residual cancer was found in the mastectomy specimens in 52% after generous excisional biopsies. Sixteen percent of patients with minimal infiltrating cancer and clinically negative axillae had micrometastases (2mm or less) in axillary nodes. The crude survival rate free of disease was 93 of 95 patients (98%) at 5 years, and 42 of 44 patients (95%) at 10 years. There were no local recurrences. No postoperative radiation was used on these patients. Modified radical mastectomy is recommended as the ideal treatment for minimal breast cancer as it yields excellent long term salvage, complete local control, and is more acceptable cosmetically than the classical radical mastectomy. It is to be preferred over extended lumpectomy (tylectomy) with radiation therapy since it avoids the potential long‐term carcinogenic effects of ionizing radiation. The excellent results obtained by adequate treatment of minimal breast cancers attest to the need for reliable mass screening techniques to detect occult, asymptomatic breast cancer, and for the availability of these techniques to the public at large.

Infiltrating lobular carcinoma of the breast.

Three hundred and fifty‐four patients with histologically proven infiltrating lobular carcinoma of the breast were seen at Memorial Hospital, New York City, between 1956 and 1970. This comprised 5.8% of all breast cancers seen during this interval. Infiltrating lobular breast cancer is found less frequently in the Negro female—3.7% vs. 5.8% for all breast cancer. Histologic differentiation from infiltrating duct carcinoma may be difficult. Clinical diagnosis is often complicated by its gross similiarty to “localized mastitis.” Bilaterality is more frequent with infiltrating lobular carcinoma—23% vs. 16% for infiltrating duct carcinoma. Infiltrating lobular carcinoma is lethal in its behavior, 5‐ and 10‐year salvage rates, after similar therapy, being slightly below those for infiltrating breast carcinoma generally. During its in‐situ stage, lobular carcinoma can be cured consistently by total mastectomy. When definitive surgical therapy is delayed until infiltrating breast cancer has developed, the patient is exposed to a greater long‐term risk because of the uncertain prognosis of infiltrating lobular carcinoma.

Breast cancer presenting as an axillary mass.

Experience with breast cancer presenting as an axillary mass in 42 patients has been reviewed according to initial clinical findings, treatment and survival. In the absence of an obvious inflammatory lesion, an axillary node may prove to be the first sign of breast cancer. It has been demonstrated that such a node should be biopsied and if positive for adenocarcinoma, a radical mastectomy performed presuming other primary sites have been ruled out. The survival rate after surgery in this group of patients is better than in those who present with a palpable breast mass and have axillary metastases.

Bilateral breast cancer.

The bilateral nature of breast cancer is generally accepted. Early detection of second primary breast cancers through repeated physical and x‐ray examinations is difficult and uncertain. A significant number of occult second primary breast cancers have been detected in their earliest stages through generous surgical biopsy of the opposite breast at the time of initial mastectomy for a proven breast cancer. Some of these early cancers were not detected by either careful physical examination or adequate x‐ray mammography. Biopsy of the contralateral breast is a minor nondeforming operation which is well‐accepted by the patient. The second mastectomy is more readily accepted by the patient after a positive biopsy has been obtained. Simultaneous, generous excisional biopsy of the opposite breast at the time of initial mastectomy for breast cancer represents a practical approach to the problem of bilateral breast cancer. However, a negative biopsy of the opposite breast does not rule out the possibility of subsequent development of a new primary in this breast at a later date. All patients undergoing mastectomy for breast cancer should be followed closely, with particular emphasis on the opposite breast. There is an urgent need for the development of more efficient methods for detecting early breast cancer, preferably, during its long, silent noninfiltrating phase of development.

The problem of carcinoma developing in a fibroadenoma: recent experience at Memorial Hospital.

Fourteen new cases of unsuspected carcinoma developing in fibroadenomas are reported with a detailed analysis of their preoperative findings; histopathology, the results of varying surgical procedures and a three month to twenty‐six year follow‐up. The majority of lesions were lobular carcinoma in situ (71%) and 29% of all cases were found to have carcinoma of the contralateral breast. Our study suggests that for invasive carcinoma within a fibroadenoma complete mastectomy is warranted in virtually all instances while noninvasive disease treated by complete mastectomy is essentially curative. Contralateral breast biopsy at the time of diagnosis with a careful life‐time follow‐up are appropriate because of the high risk of contralateral invasive coarcinoma. There seemed to be no evidence of striking or unusual epithelial hyperplasia in the breast tissue adjacent to fibroadenomas that contained carcinoma suggesting that the carcinomas are not intrinsically different from those not related to fibroadenomas. Cancer 43:563–567, 1979.

Have changing treatment patterns affected outcome for operable breast cancer? Ten-year follow-up in 1288 patients, 1965 to 1978.

From 1965 to 1978, 1288 patients with primary operable breast cancer were treated by the senior author, using extended radical (ERM), radical (RM), and modified radical (MRM) mastectomy operations exclusively. Results were analyzed for trends in overall and disease-free survival, and patterns of local and distant relapse, the years 1965 to 1970 versus 1971 to 1974 versus 1975 to 1978. Significant changes (p < 0.00001) from 1965 to 1978 included progressively earlier stage of disease, less frequent use of RM and ERM, a decline in the use of postoperative radiotherapy, and the introduction in 1975 of multidrug adjuvant chemotherapy. Ten-year disease-free survival rates improved significantly for all patients (by 11%, p = 0.00004) and for node-negative (by 12%, p = 0.0024), node-positive (by 8%, p = 0.012), clinical stage II (by 15%, p = 0.0022), and pathologic stage II (by 12%, p = 0.016) disease. Ten-year local recurrence for all patients was 3% (local only) and 2% (local with distant metastasis), and survival from date of recurrence for all patients failing treatment increased two times (p < 0.0001) for patients treated most recently. As the primary surgical treatment of breast cancer continues to become more moderate, the promise of systemic adjuvant therapies can be realized only with continued emphasis on earlier diagnosis and maximal local control of disease.

Immunobiology of Operable Breast Cancer: An Assessment of Biologic Risk by Immunoparameters

The concept of whether immune function was related to risk of recurrence was examined in patients with operable breast cancer in whom careful clinical and pathologic staging had been performed. Patients were classified according to the risk of recurrence. The “low risk” group included patients with minimal breast cancer, noninfiltrating cancer, or infiltrating cancer <1 cm with negative nodes. The “high risk” group included patients with lesions >1 cm or who had ≥4 nodal metastases or who had macrometastases at Level II or III (apex). In the “intermediate risk” group were patients with infiltrating cancer <1 cm or with <4 nodal metastases at Level 1 only. Immune reactivity was assessed by skin tests, by measurement of absolute lymphocyte count, T and B cells, lymphocyte stimulation by mitogens and a battery of common antigens, serum immunoglobulins and complement levels. There were 134 patients with operable breast cancer and 63 patients with benign breast lesions. The breast cancer patients showed minimal or no impairment of DNCB skin tests. Only patients with nodal metastases showed a slight but not significant impairment of DNCB responses (80% were DNCB positive compared to 90% in the controls). The lymphocyte responses to mitogens were normal in the breast cancer patients, but there was a significant depression of lymphocyte responses to certain recall antigens such as Candida albicans and E. coli. The absolute lymphocyte count and the T cell counts were normal, but B cells bearing complement receptors were decreased and B cells bearing surface immunoglobulins were increased in the breast cancer patients. Analysis of immune function according to the pathologic stage of disease “risk of recurrence” categories showed no correlation with skin tests or lymphocyte levels. A striking and paradoxical finding was the demonstration that patients with “low risk” cancer overall had markedly lower responses to the battery of stimulating mitogens and antigens than found in patients with “high risk” or “intermediate risk” disease. Only the lymphocyte response to PHA showed a significant linear correlation with increasing pathologic stage or “risk of recurrence.” Current evidence from this study suggests that PHA response is markedly influenced by the primary tumor burden and thus indirectly reflects the risk of recurrence.