Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18.

PURPOSE: To determine whether preoperative doxorubicin and cyclophosphamide (AC) permits more lumpectomies to be performed and decreases the incidence of positive nodes in women with primary breast cancer. PATIENTS AND METHODS: Women (n = 1,523) were randomized to National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18; 759 eligible patients received postoperative AC and 747, preoperative AC. The clinical size of breast and axillary tumors was determined before each of four cycles of AC and before surgery. Tumor response to preoperative therapy was clinically complete (cCR), partial (cPR), stable (cSD), or progressive disease (cPD). Tissue from patients with a cCR was evaluated for a pathologic complete response (pCR). RESULTS: Breast tumor size was reduced in 80% of patients after preoperative therapy; 36% had a cCR. Tumor size and clinical nodal status were independent predictors of cCR. Twenty-six percent of women with a cCR had a pCR. Clinical nodal response occurred in 89% of node-positive patients: 73% had a cCR and 44% of those had a pCR. There was a 37% increase in the incidence of pathologically negative nodes. Before randomization, lumpectomy was proposed for 86% of women with tumors < or = 2 cm, 70% with tumors 2.1 to 5.0 cm, and 3% with tumors > or = 5.1 cm. Clinical tumor size and nodal status influenced the physician's decision. Overall, 12% more lumpectomies were performed in the preoperative group; in women with tumors > or = 5.1 cm, there was a 175% increase. CONCLUSION: Preoperative therapy reduced the size of most breast tumors and decreased the incidence of positive nodes. The greatest increase in lumpectomy after preoperative therapy occurred in women with tumors > or = 5 cm, since women with tumors less than 5 cm were already lumpectomy candidates. Preoperative therapy should be considered for the initial management of breast tumors judged too large for lumpectomy.

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Influence of estrogen receptors on survival and recurrence in patients with breast cancer without lymph node metastases.

A retrospective chart review was conducted to determine the prognostic effect of estrogen receptor (ER) protein in patients with node-negative operable breast cancer. One hundred nine patients with breast cancer whose tumors underwent ER analysis and whose lymph node negativity was established histologically were studied. Based on life-table analysis, the overall survival at six years was 92.7% for ER-positive patients, 95.3% for ER-negative patients, and 94.4% for ER-borderline patients. The disease-free survival was 83.3%, 92.8%, and 71.4%, respectively. Survival and disease-free survival were also correlated to menopausal status. The difference in survival was not statistically significant at six years. We conclude that in node-negative primary operable breast cancer, ER status should not be used as a discriminant for adjuvant treatment.

The learning curve for sentinel node biopsy in breast cancer: practical considerations.

HYPOTHESIS: Performance of sentinel node biopsy (SNB) instead of full axillary lymph node dissection (ALND) by inexperienced surgeons will lead to understaging of some women with breast cancer and increased costs. DESIGN: A decision analysis model was used to investigate the implications of SNB vs. full ALND during the learning phase (60-80 procedures). This model simulates a randomized trial of 10000 women in each arm. Data regarding the learning curve were obtained from published series. MAIN OUTCOME MEASURES: Percentage of women with inaccurate staging of their breast cancer, overall survival, quality-adjusted survival, and potential costs of SNB vs ALND. RESULTS: Performance of SNB instead of ALND results in inability to locate a sentinel node in 38% of attempts during the learning phase (compared with 10% in later cases) and understaging in 12% of patients during the learning phase (compared with 0% in later cases). This understaging is associated with a small decrement in survival (1%-2%) and an increased risk of axillary recurrence. Sentinel node biopsy is cost-effective only when the ability to detect sentinel nodes exceeds 80%; and the cost of SNB is less than 50% of the cost of ALND. CONCLUSIONS: To ensure accurate staging of patients with breast cancer, all surgeons should perform full ALND while learning SNB techniques. Only after documentation of accuracy of SNB (sensitivity >90%) should full ALND be omitted for women with negative sentinel nodes.

Chemotherapy drug dose alteration due to radiation therapy in an adjuvant situation in breast cancer.

Fifty-six patients with T1-T3 and T2-T3 N0 medial lesions of breast carcinoma were randomized after modified radical mastectomy to receive either cytoxan, methotrexate, 5-fluorouracil (5-Fu) (CMF) chemotherapy for 1 year (group A) or CMF for 1 year and postoperative radiation therapy (group B). Thirty-two patients received chemotherapy alone and 25 patients received both chemotherapy and radiation therapy. Twenty-five of 32 group A patients (median age 52) and 20/24 group B patients (median age 50) were evaluable. Leukopenia was the major cause of drug dose reduction in both groups. In group A, 4/25 patients (16%) had leukopenia at less than the 2500 level, whereas 8/20 (40%) group B patients had leukopenia at the same level. If 70% of all three drug dosages are considered as adequate chemotherapy, 21/25 (84%) patients received adequate chemotherapy in group A, and 10/20 (50%) in group B (p approximately equal to 0.029 from contingency table). It appears that radiation therapy in postmastectomy patients hinders adequate drug dose delivery in an adjuvant setting.

Early breast cancer detected by mammography. Marshfield Clinic experience.

Use of mammography in asymptomatic women does discover breast cancer at an earlier point in development, as measured by size, invasiveness, and nodal involvement. The integration of mammography into routine periodic evaluation of asymptomatic women over 35 years of age should diminish the threat of breast cancer.

Definitive breast cancer surgery as an outpatient: a rational basis for the transition.

The transition of definitive breast cancer surgery to an outpatient setting cannot be done without some major philosophical and technical changes on the part of the surgeon. This paper outlines the changes in the author's practice made over two decades demonstrating that this transition has had no effect on outcome. Definitive surgical care for breast cancer can occur in a cost-effective fashion totally on an outpatient basis.

Comparison of estrogen receptor levels in primary and regional metastatic carcinoma of the breast.

The estrogen receptor (ER) level in carcinoma of the breast is a useful predictor of response to hormonal therapy. Metastatic disease may not have the same level of ER as the primary. In a series of 37 patients who had simultaneous ER determination in both primary neoplasm and regional nodal metastasis there was 81% agreement. The true ER character of the tumor would have been missed in seven patients if only the primary tumor had been sampled. The possible reasons for this discrepancy are discussed. We feel that the nodal metastatic deposit may reflect the true nature of the ER status because it represents a purer concentration of tumor cells as well as representing the aggressive element of the tumor.

Fibrosarcoma of the colon.

Fibrosarcomas of the colon are extremely rare. This is the report of a patient with fibrosarcoma of the transverse colon who had perforation and peritonitis.

Localization of occult breast lesions.

Localizing nonpalpable suspicious lesions seen by mammography is a challenge to the surgeon. Using a previously reported technique we report our experience in 66 needle localization procedures for nonpalpable lesions of which fourteen were carcinoma. We emphasize the ease and accuracy of this technique with minimal loss of breast substance.

Carcinoma of the breast with pseudosarcomatous metaplasia.

Twenty-six cases of breast carcinoma demonstrating pseudosarcomatous metaplasia are described, and their clinical and pathologic aspects are correlated. The metaplastic elements include mature and immature bone, cartilage, myxoid stroma, loose fibromyxoid and dense spindle-cell stroma, and anaplastic stroma with giant cell features. Light and electron microscopic examination demonstrated an orderly sequence of transformation and dedifferentiation of epithelial cells to become undifferentiated mesenchymal cells. These tumors are more aggressive than purely epithelial carcinomas. The overall survival rate was 44%. Five-year survival figures for TNM Stages I, II, and III lesions were 56%, 26%, and 18%, respectively. The incidence of lymph node metastasis was 25% despite the large size of many of these tumors. Systemic metastases replicated the range of metaplastic elements seen in the primary site. Patients with tumors composed predominantly of pseudosarcomatous elements had worse prognoses than those with predominantly epithelial components (28% versus 62%, 5-year survival).

Improved survival in the treatment of advanced Hodgkin's disease at a nonuniversity institution (1970-1979).

From 1970 through 1979, 89 patients with Hodgkin's disease were treated at the Marshfield Clinic/St. Joseph's Hospital. After the pathologic material was reviewed, the patients were analyzed to compare Group I (1970-1973) with Group II (1974-1979). Demographic characteristics in the two groups were similar. In the decade, 76% of patients achieved complete remission. In advanced-stage disease, 50% of patients achieved complete remission in Group I compared with 68% in Group II. At 5 years, 50% of patients were alive without COPP (cyclophosphamide, vincristine, procarbazine, prednisone) chemotherapy; with this treatment, 75% of patients survived (P = 0.02). There was improved survival comparing Group I (56% at 5 years) with Group II (76% at 5 years) patients with advanced disease (P = 0.004). More aggressive combination chemotherapy (COPP) was related to the improvement in survival (P less than 0.001). The advances in treatment made by cooperative groups and universities are being transferred to nonuniversity institutions, with appropriate improvement in survival of Hodgkin's disease.

Results of a 400-patient carcinoembryonic antigen second-look colorectal cancer study.

Four hundred patients with resectable colon and rectal cancers were operated on by 37 surgeons at 31 institutions. Patients were monitored with carcinoembryonic antigen (CEA) level determinations and clinical examinations. One hundred thirty patients had recurrences, and 75 were reoperated on, with 43 reoperations CEA-directed and 32 clinically directed. Two of 75 died within 1 month after the second operation. Twenty-two second-look patients remain free of disease 5 years after their second operation. The highest resectability of recurrent cancer occurred in patients with a CEA level below 11 ng/ml in whom the CEA level was determined at intervals of 1 to 2 months.