Alfred A. Fracchia

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.

Axillary micro- and macrometastases in breast cancer. Prognostic significance of tumor size

Recurrence and survival data at 10 years were examined for 147 women with single axillary lymph node metastases found in a modified radical or standard radical mastectomy. The cases were identified through a review of all patients with primary operable breast cancer treated at Memorial Hospital from 1964 to 1970. The patients were stratified into groups according to size of the primary tumor and of the metastatic deposit (micro < 2 mm; macro > 2 mm) as well as level of the positive node. In the entire series, there was a significantly poorer prognosis among those patients with single macrometastases (30/ 77 patients: 39% recurrence rate) when compared with those having micrometastases (17/70 patients: 24% recurrence rate). A major prognostic difference emerged after stratification by tumor size. Within the first six years of the follow-up period, T| patients with negative nodes and those with single micro-metasteses had similar survival curves, significantly better than those with macrometastases. However, at 12 years, the survival rate of those patients with either a micro- or macrometastasis was nearly identical, and significantly worse than for those patients with negative lymph nodes. On the other hand, among women with primary tumors 2.1–5.0 cm (T2), patients with negative lymph nodes or single micrometastases had survival curves that did not differ significantly throughout the course of the follow-up period. Both had an outcome significantly better than observed for patients with macrometastases. These findings have important implications for our understanding of the clinical behaviour of breast cancer and for the stratification of patients entered into randomized treatment trials

Intrapleural chemotherapy for effusion from metastatic breast carcinoma

Efficacy of thoracentesis with the instillation of nitrogen mustard or thio‐TEPA for malignant pleural effusions due to metastatic mammary carcinoma is investigated. One hundred and thirty‐eight patients were evaluated, of whom 93 were treated by aspiration or intercostal tube drainage of the effusion followed by instillation of a cytotoxic agent. The remaining 45 patients received similar intrapleural chemotherapy and subsequent systemic cytotoxic agents several months later. Thirty‐eight (27.5%) of the total patients in this study demonstrated an objective response with an average duration of 8.8 months. Subjective improvement was observed in 73 (53%). Rate and duration of response to instillation of nitrogen mustard and thio‐TEPA were similar. The use of a recently devised weighted intercostal tube with the same alkylating agents significantly improved the results.

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.

Indications for castration and adrenalectomy for advanced breast cancer.

The case records of over 1,000 female patients with advanced breast cancer were reviewed. Of these, 527 were treated by therapeutic castration and 500 underwent adrenalectomy or combined oophoroadrenalectomy. The careful attention to the duration of the clinically‐free interval and the location and extent of metastatic involvement is important. Regression by local radiotherapy prior to castration and the effect of castration before adrenalectomy were also of value. Until such time as a reliable test is found, we are still dependent on these clinical findings as the most accurate determinants for the selection of patients most likely to benefit from palliative procedures. Those considered unsuitable for endocrine ablation may be improved by the early use of alternative methods of treatments such as hormone therapy, cytotoxic agents, or their combinations.

Simple excision or biopsy plus radiation therapy as the primary treatment for potentially curable cancer of the breast

This retrospective study compares in detail the pretreatment clinical findings and therapeutic results following initial treatment of 77 patients by various types of biopsy and major radiation therapy with those in a similar number having only radical surgery and a second group treated by radical mastectomy and postoperative irradiation. Of the 77 having biopsies, 27 had an aspiration, 33 incisional and 17 exeisional biopsy or what may be considered a simple excision. The amount of primary irradiation delivered to these patients varied considerably but the best results were obtained following a total dosage of 6,000 rads or more. While none of these methods of treating primary operable and infiltrating carcinoma of the breast cured all the patients, there were significant differences in therapeutic results. Those subjected to a radical mastectomy with or without postoperative irradiation had a longer clinically free interval, a lower incidence of local recurrence, and a higher total survival rate than the patients treated by various biopsies and primary irradiation. The physical intolerance to a radical breast operation has greatly decreased, but there is now an increased emphasis on limited surgery by a few doctors so as to preserve feminine appearance. While this is desirable, there remains an essential need for more accurate and reliable means to select patients for such treatment in order to obtain therapeutic results equally good as those which follow radical mastectomy.

Systemic chemotherapy for advanced breast cancer.

During a 20‐year period, 377 women with primary advanced or metastatic breast cancer were treated systemically by various chemotherapeutic agents and were considered suitable for a detailed analysis of therapeutic results. Fifty‐five (15%) of these patients experienced objective remission of palpable or demonstrable disease for 2 months and 10% for 6 months, but 19.6% died within one month after the initiation of treatment. It should be noted that 271 of the total patients in this study had been previously treated by additive or ablative hormone therapy and, at the time chemotherapy was given, a majority had multiple metastases and, in some instances, involvement of vital organs. Regardless of the type of chemotherapy, as well as the initial maintenance or total dosage, the poorest therapeutic results were obtained when the metastases were located in the bones, brain, or lungs with lymphangiectatic involvement and the liver with jaundice or abdominal ascites. The best results were observed when the cancer was located in nonvital soft tissues as well as nodular pulmonary metastases and the liver without associated functional complications. While there are controversial opinions regarding the need for toxic side effects in order to produce objective remissions, in our observations, dosages just below the level of toxicity in most instances produced almost equal therapeutic results. If there were failures to subtoxic doses, better results were obtained by using a different cytotoxic agent rather than increasing the amount of the initial drug. In this review, very few patients received simultaneously multiple anticancer drugs, and whether or not this would produce better results than successive use of single cytotoxic agents remains to be evaluated. The determination of which chemotherapeutic agent is most effective regarding the anatomical site of the breast cancer cells remains an unsolved problem. In this nonrandomized study, comparative results suggested that objective responses declined in the following order: methotrexate, Leukeran, Thio‐TEPA, Velban, 5‐fluorouracil, Cytoxan, and nitrogen mustard. It should be noted that the number of patients treated by each of these compounds varied considerably, and this may in part account for the differences in response rates. When chemotherapy was combined simultaneously with other palliative measures, the results in the chemotherapy group were improved but infrequently exceeded the response rates of those following the use of additive or ablative hormone therapy alone. While chemotherapy has contributed to the symptomatic and objective palliation of many patients with advanced breast cancers, our observations suggest that with few exceptions it should be used to supplement rather than to replace other measures. The exceptions apply to those patients who would be unable to tolerate other palliative procedures because of physical conditions from anatomical sites of metastases, advanced age, or unrelated complications.