Showing papers by "Bernard Fisher published in 1985"

Five-Year Results of a Randomized Clinical Trial Comparing Total Mastectomy and Segmental Mastectomy with or without Radiation in the Treatment of Breast Cancer

Abstract: In 1976 we began a randomized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors less than or equal to 4 cm in size. The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor. Women were randomly assigned to total mastectomy, segmental mastectomy alone, or segmental mastectomy followed by breast irradiation. All patients had axillary dissections, and patients with positive nodes received chemotherapy. Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy, with or without breast irradiation, resulted in disease-free, distant-disease-free, and overall survival at five years that was no worse than that after total breast removal. In fact, disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy (P = 0.04), and overall survival after segmental mastectomy, with or without radiation, was better than overall survival after total mastectomy (P = 0.07, and 0.06, respectively). A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years, as compared with 72.1 per cent of those receiving no radiation (P less than 0.001). Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free (P less than 0.001), although both groups received chemotherapy. We conclude that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm, provided that margins of resected specimens are free of tumor.

Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation

Abstract: In 1971 we began a randomized trial to compare alternative local and regional treatments of breast cancer, all of which employ breast removal. Life-table estimates were obtained for 1665 women enrolled in the study for a mean of 126 months. There were no significant differences among three groups of patients with clinically negative axillary nodes, with respect to disease-free survival, distant-disease--free survival, or overall survival (about 57 per cent) at 10 years. The patients were treated by radical mastectomy, total ("simple") mastectomy without axillary dissection but with regional irradiation, or total mastectomy without irradiation plus axillary dissection only if nodes were subsequently positive. Similarly, no differences were observed between patients with clinically positive nodes treated by radical mastectomy or by total mastectomy without axillary dissection but with regional irradiation. Survival at 10 years was about 38 per cent in both groups. Our findings indicate that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival. The data also demonstrate that the results obtained at five years accurately predict the outcome at 10 years. We conclude that the variations of local and regional treatment used in this study are not important in determining survival of patients with breast cancer.

Lumpectomy and axillary dissection for breast cancer: surgical, pathological, and radiation considerations.

Abstract: Recently, the first results were disclosed from a trial carried out by the National Surgical Adjuvant Breast and Bowel Project (NSABP) to evaluate the efficacy of breast conservation. These observations indicate that lumpectomy and axillary dissection plus radiation can be employed instead of total mastectomy for the treatment of a large proportion of women with primary breast cancer. The present report describes the technique of operation (lumpectomy), how the pathological examination of the resected specimen is carried out, and the manner in which radiation therapy is administered to the operated breast. The methodologies are those utilized in more than 1,200 women who for almost a decade have been participants in the NSABP study. It is emphasized that the outcome of patients exposed to breast preservation relates to the expertise of the surgeon, pathologist, and radiation and medical oncologists. The orchestration of care that will result in a satisfactory cosmesis and control of disease in the breast is more complex than is necessary for carrying out a mastectomy. Above all it is emphasized that, although the Halstedian concept for cancer surgery has been displaced, that change does not provide the imprimatur for haphazard surgery.

The revolution in breast cancer surgery: science or anecdotalism?

Abstract: During the past 15 to 20 years, there have resulted revolutionary changes in the local/regional management of primary breast cancer Why have those changes come about? Has science played a role or have they been entirely related to the experiences of a few who have “tampered with tradition” for some nebulous reason? This report traces the pathway of change from Halsted's time to the present and attempts to point out wherever possible the relation of these changes to science and/or to “anecdotalism” It traces the origins of the Halstedian hypothesis of cancer management, the reasons for its perpetuation, and the clinical challenges to it which were really not challenges at all A description of laboratory and clinical research in the 1960's which led to an alternative hypothesis is presented, as is a description of how clinical trials tested the alternative hypothesis The results of those trials, recently reported, lend support to a concept of surgery for cancer which embodies biological principles rather than the mechanistic and anatomical principles of the past A brief discussion is provided relative to how cancer surgery interrelates with other modalities and the article concludes with the author's concept of a surgical oncologist

Tissue mast cells in breast cancer.

Abstract: The total number of mast cells and the number of such cells observed within and at the periphery of invasive breast cancers from 424 patients enrolled in protocol 4 of the National Surgical Adjuvant Breast Project were correlated with 38 other pathologic and 6 clinical features. High total mast cell counts as well as those within and at the periphery of the cancers were found to be significantly (p≤.05) associated with a patient age less than 50 years and the degree of tumor lymphoid cell reaction. The latter has also been found to be related to young age and other pathologic characteristics related to mast cell content. This suggests that the mast cells may simply represent another cell type of this reactive change. No differences in 10 year disease-free survival were detected in patients without mast cells and those exhibiting varying numbers of such cells. This information indicates that identifiable mast cells do not represent a prognostic pathologic discriminant in patients with breast cancer. However, this does not unequivocally exclude a role of mast cell secretory products, since only intact and not degranulated or disrupted forms of these cells can be counted.

Reappraisal of breast biopsy prompted by the use of lumpectomy. Surgical strategy.

Abstract: NOT LONG ago, a one-stage procedure was standard for diagnosing and treating breast cancer. While such a course of action has decreased in popularity, it is still frequently employed. With that strategy, excisional biopsy, frozen section diagnosis, and mastectomy, if the tissue is malignant, are sequentially performed with general anesthesia. Since the approach best fulfills the Halstedian priniciples governing cancer surgery, it cannot be criticized if the surgeon continues to adhere to those precepts. When the one-stage procedure is used, it is not so critical that the biopsy completely remove all of the tumor since mastectomy immediately follows a positive biopsy finding. Under those circumstances, the role of the pathologist is to determine the diagnosis and not to decide whether the margins of the biopsy specimen are tumor free. When there is a high index of suspicion that the lesion is cancer, the biopsy is usually planned with little or

Limited surgical management for primary breast cancer: a commentary on the NSABP reports.

Abstract: This report presents an overview of findings from 2 interrelated studies carried out during the past 15 years by the National Surgical Adjuvant Breast and Bowel Project to determine the efficacy of alternative local and regional treatments of primary breast cancer. Findings from the first clinical trial, begun in 1971 involving 1,665 women, indicate that after 10 years of follow-up there are no significant differences in disease-free survival, distant disease-free survival, or survival among patients treated by radical mastectomy or total mastectomy with and without radiation. The findings also indicate that radiation of internal mammary nodes in patients with inner quadrant lesions does not improve survival and that results obtained at 5 years accurately predict the outcome through 10 years. The second clinical trial, implemented in 1976 and accruing 1,843 women, demonstrates that after 5 years, treatment by segmental mastectomy (lumpectomy) with or without radiation results in disease-free, distant disease-free, and overall survival at least equivalent to, and in certain aspects better than, that achieved after total breast removal. Whereas 92% of those treated with radiation remained free of breast tumor at 5 years, when breast radiation was not employed, 72% (p<0.001) were without tumor reoccurrence. In positive-node patients, 98% of those radiated remained tumor free, whereas only 64% of those receiving no radiation were free of tumor although both groups received chemotherapy. While the clinical significance of these findings is obvious, their biological importance has received less attention. When considered in conjunction with other laboratory and clinical investigations, they lend no support for the anatomic and mechanistic precepts that have dictated thinking relative to metastasis production and have influenced surgical thinking. Clinical issues have arisen as a consequence of the 2 studies, particularly the second. Should a mastectomy be performed when lumpectomy specimen margins are involved with tumor? How should tumor reoccurrence in the ipsilateral breast following lumpectomy be managed? Can lumpectomy be employed for subareolar tumors or for tumors ≥4 cm? How extensive need radiation therapy be following lumpectomy? We have commented on all of these issues and have presented our current thinking regarding the management of patients in whom they arise.

Biologic considerations regarding the one and two step procedures in the management of patients with invasive carcinoma of the breast.

Abstract: Investigation of the biologic significance of delay between biopsy and mastectomy was performed upon women with invasive carcinoma of the breast in protocol four of the NSABP. Since the period of delay was two weeks or less in approximately 75 per cent, no comment concerning the possible effects of longer periods can be made. Life table analyses failed to reveal any difference in ten year survival rates between patients undergoing radical mastectomy management by the one and two step procedures. Similarly, no difference in adjusted ten year survival rate was observed between women managed by the two step procedure who did or did not have residual tumor identified in the mastectomy specimen after the first step or biopsy. Importantly, the clinical or pathologic stages, sizes of tumor or histologic grades were similar in women managed by the one and two step procedures minimizing selection bias. The material used also allowed for study of the possible causative role of biopsy of the breast on the development of sinus histiocytosis in regional axillary lymph nodes. No difference in degree or types of this nodal reaction could be discerned in the lymph nodes of the mastectomy specimens obtained from patients who had undergone the one and two step procedures. This finding indicates that nodal sinus histiocytosis is indeed related to the neoplastic process, albeit in an undefined manner, rather than the trauma of biopsy per se as has been suggested. These results do not invalidate the use of the one step procedure in the management of patients with carcinoma of the breast. Indeed, it is highly likely that it will be commonly used now that breast-conserving operations appear to represent a viable alternative modality for the primary surgical treatment of carcinoma of the breast. Yet, it is apparent that the one step procedure will be performed for technical and practical rather than biologic reasons.

Adjuvant chemotherapy in stage II breast cancer: a brief overview of the NSABP clinical trials.

Abstract: Since 1972 the National Surgical Adjuvant Breast and Bowel Project (NSABP) has completed 5 adjuvant chemotherapy protocols into which over 3,500 histologically nodepositive patients have been entered; data for this review are derived predominantly from the first 3 studies. Each study was performed sequentially with the intent of identifying patient subsets responding to 1, 2, or 3 chemotherapeutic agents. Comparison of disease-free survival in patients receiving l-phenylalanine mustard (L-PAM) or placebo after 10 years of follow-up disclosed that L-PAM was beneficial in patients up to 49 years of age, but not in women ⩾50 years. Further analysis indicated that the subset of patients ⩽49 years with 1–3 positive nodes sustained the greatest increment in disease-free survival with single-agent L-PAM. The addition of 5-fluorouracil (5-FU) to L-PAM was superior to L-PAM alone in patients ⩾50 years of age, particularly those with ⩾4 positive nodes. This effect became attenuated after 6 years of follow-up. The 3-drug regimen of L-PAM, 5-FU, and methotrexate failed to provide a benefit over and above that achieved by the L-PAM-5-FU combination in all subsets examined. Two further NSABP protocols are described in which the addition of Adriamycin® to L-PAM and 5-FU is addressed. The rationale for the current generation of NSABP adjuvant chemotherapy trials using short intensive Adriamycin® and cyclophosphamide regimens is discussed. The results continue to underscore the heterogeneous response to chemotherapy demonstrated by patient subsets characterized on the basis of age and nodal status.

Adjuvant tamoxifen and chemotherapy in stage II breast cancer: interim findings from NSABP protocol B-09.

Abstract: Data are presented from a prospective clinical trial in which 1,891 patients with histologically confirmed stage II breast cancer were randomized to receive adjuvant therapy consisting of 1-phenylalanine mustard and 5-fluorouracil (PF) with and without tamoxifen (T). The findings indicate that the benefit previously noted for the addition of tamoxifen at 2 and 3 years' mean follow-up is still apparent at 4 years. Although the tamoxifen-containing regimen prolongs disease-free survival and survival, this effect is not uniform and is dependent on patient age and tumor receptor content. Only those patients ⩾ 50 years of age demonstrated a benefit from the addition of tamoxifen to chemotherapy. The benefit was influenced by the degree of quantitative tumor receptor content. Patients ⩽ 49 years of age failed to demonstrate a prolongation in disease-free survival with tamoxifen even when the tumor estrogen receptor content was ⩾100 fmol. Not only was there no benefit attributable to tamoxifen in patients ⩽49 years, if the tumor progesterone receptors were <10 fmol there was a significant diminution in disease-free survival and survival. The results continue to indicate that the response to PFT therapy is heterogeneous in that only specific patient subsets demonstrate a salutary effect. Whether this phenomenon of heterogeneity is unique to the PFT combination or is an intrinsic biological property of stage II breast cancer remains to be ascertained.

Optimal surgical approaches to the local management of early breast cancer. A panel discussion.

Abstract: In recent years, a trend has developed toward more conservative surgery for early breast cancer, often in combination with axillary dissection or sampling and with radiotherapy. Here, three prominent breast cancer surgeons discuss the proper role of these procedures and several areas of contention concerning them.