Prognosis of patients with bilateral carcinoma of the breast.

Ninety-five patients with bilateral carcinoma of the breast treated with mastectomy (60 patients), conservation of the breast (17 patients), or both (18 patients), were studied. Cumulative five year local control rates for the 138 mastectomies was 94 percent and for the 52 breast conservations, 90 percent. Distant metastases appeared in one-third of the patients but one-half of them occurred beyond 60 months. Cumulative five year distant disease-free survival rate measured from treatment for the second carcinoma was 74 percent. Second carcinomas were diagnosed at significantly earlier stage than first carcinomas--28 percent of first carcinomas were stage I compared with 43 percent of second carcinomas (p < 0.05). Distant recurrence-free survival rates for metachronous carcinomas were better then for synchronous carcinomas, but this difference can be attributed to earlier overall staging of metachronous carcinomas. The interval between the diagnosis of first and second carcinomas had a profound effect on outcome for second carcinomas--cumulative five year distant recurrence-free survival rate of patients with second carcinomas diagnosed within five years was 58 percent compared with 95 percent for patients diagnosed more than five years after the first carcinoma.

Surgery for nonpalpable breast lesions.

Nonpalpable lesions detected on mammograms were localized in 475 women between 1976 and 1988 by means of the spot method. A malignant neoplasm was noted in 149 patients (31%), including 69 (33%) of 206 with clusters of microcalcifications, 16 (41%) of 39 with calcifications associated with densities and 64 (28%) of 230 with nonpalpable masses. Infiltrating lesions were present in 89 (60%) of 149 patients. Among women with infiltrating lesions who had axillary dissection, 14 (21%) of 67 had positive nodes. In younger women, microcalcifications were more likely to represent neoplasms, masses frequently represented invasive tumors. Among patients with invasive malignant neoplasms who had calcifications, 39% had positive axillary lymph nodes. Spot localization, rather than monitoring, seems appropriate in young women with microcalcifications suggestive of malignant neoplasms and older patients with nonpalpable masses to achieve earlier and more effective treatment of biologically significant occult neoplasms.

Combination chemotherapy with mastectomy or radiotherapy for stage III breast carcinoma: a Cancer and Leukemia Group B study.

One hundred thirteen evaluable patients with previously untreated stage III breast carcinoma were treated with three monthly cycles of cyclophosphamide (CYC), doxorubicin (DOX), 5-fluorouracil (5-FU), vincristine (VCR), and prednisone (PRED) (CAFVP). Subsequently, 91 (81%) were deemed operable. Patients were then randomized to receive surgery or radiotherapy (RT) to determine which of these modalities afforded better local tumor control. All patients also received 2 additional years of CAFVP in a further attempt to eradicate local disease and systemic micrometastases. Forty-one of the randomized patients have relapsed. Approximately half of the initial relapses in each arm were local. The overall duration of disease control was similar following either modality, with a median of 29.2 months for surgery patients and 24.4 months for RT patients. Similarly, there was no major difference in survival related to randomized treatment with an overall median of 39 months (median follow-up 37 months). Pre- or perimenopausal status and inflammatory disease were associated with shorter disease control and survival. Treatment was generally well tolerated and toxicity was acceptable. This study demonstrates that prolonged control of stage III breast carcinoma can be achieved with combined modality therapy in which cytotoxic chemotherapy precedes and follows treatment directly primarily at the breast tumor, using either surgery or RT. Nevertheless, new regimens must be designed if significant advances that may lead to the cure of this disease are to be achieved.

Diagnosis of breast masses by physical examination, fine-needle aspiration, and excision biopsy.

The technique of obtaining material from breast masses for cytologic evaluation is described. Results obtained after aspiration of 950 solid lesions are presented. The sensitivity of the examination is 86%, the specificity 96%. The accuracy of a benign diagnosis is 97% and of a malignant diagnosis 94%.

Hyperglycemic complications associated with adjuvant chemotherapy of breast cancer. A cancer and leukemia group B (CALGB) study.

Many adjuvant chemotherapy regimens used for breast cancer include prednisone, which has the potential to cause hyperglycemia. We reviewed the results of three CALGB studies employing prednisone as part of adjuvant therapy to determine the incidence and severity of hyperglycemic complications. All treatment regimens included cyclophosphamide, methotrexate or doxorubicin, 5-fluorouracil, and vincristine in addition to prednisone. Among 1,237 evaluable patients receiving a five-drug regimen including prednisone, there were 98 patients (7.9%) who experienced any degree of hyperglycemia. Thirty patients (2.4% overall; 30.6% of those having any hyperglycemia) had severe or life-threatening degrees of hyperglycemia, including two patients whose hyperglycemia contributed directly to death. We conclude that prednisone administration as part of adjuvant chemotherapy regimens in breast cancer produces an appreciable incidence of hyperglycemia. Serum glucose levels should be monitored during therapy to help prevent the occasional severe or life-threatening episode of hyperglycemia in these patients.

Association between prognosis and hormone receptors in women with breast cancer.

Axillary node involvement, hormone receptors, tumor differentiation, and obesity have been linked to breast cancer prognosis. We have evaluated which of these factors have an independent association with disease-free survival using the Cox Proportional Hazards model. The study was carried out in 377 patients with breast cancer who underwent mastectomy and axillary node dissection between 1977 and 1984. In the univariate analysis all of the above factors were associated with differences in disease-free survival, and all entered the stepwise model. Among women with negative nodes and those with one to three positive nodes, tumor differentiation was a significant indicator of prognosis, while hormone receptors did not have prognostic significance. The opposite was noted in women with four or more involved nodes, among whom negative hormone receptors was the only significant marker of poor prognosis together with presence of obesity. Among young women node involvement and hormone receptors were significant prognostic indicators, while among older women all four variables were independent prognostic markers. These results indicate a marked heterogeneity among subgroups of women with breast cancer in relation to prognostic markers.

Modern surgical treatment of breast cancer.

Since the 1950's the treatment of breast cancer has changed substantially. This related surgery has become less disfiguring without either impairing survival or increasing recurrences. Adjuvant chemotherapy has also contributed.

Perioperative blood transfusion has prognostic significance for breast cancer.

The transfusion-induced immune suppression that prolongs kidney graft survival for transplant patients may be detrimental to patients with malignancies. We studied the relationship of blood transfusion to the disease-free survival of 169 patients with operable breast cancer who had undergone mastectomy with axillary dissection at Mount Sinai Hospital between 1964 and 1972. The cumulative 5-year disease-free survival rate for patients who had received transfusions was 51% compared with 65% for patients who had not received blood (p = 0.0210). The two groups of patients were comparable in age, stage, discharge hemoglobin values, proportion of radical mastectomies, and duration of follow-up. Admission hemoglobin values were lower and operative blood loss was higher among patients who had received transfusions, and significant survival differences were noted in relation to operative blood loss: 69% of women with estimated blood loss less than the mean of 370 ml were free of disease at 5 years compared with 50% of women with higher intraoperative losses (p = 0.0279). However, the first year after operation the association of survival with transfusion was highly significant (77% for those who had received transfusions, 94% for those who had not, p = 0.0096), whereas survival rates in relation to operative blood loss differed by only 7% during the same interval (p = 0.1182). These results indicate that perioperative blood transfusion may be a significant prognostic factor for patients undergoing mastectomy for operable breast cancer.

Chemotherapy before and after mastectomy in stage III breast cancer.

Seventeen patients with stage III breast cancer were treated by modified radical mastectomy preceded and followed by multiagent cytotoxic chemotherapy. The preoperative treatment resulted in a decrease in size of the primary tumor, facilitating the subsequent surgical procedure. There were no serious surgical complications. Wound healing was uneventful. Median disease-free survival time was 29 months and median survival time was 40+ months. Six of the 17 patients are living free of recurrence from more than 33 to more than 79 months after initial therapy.

A randomized trial of postoperative five-versus three-drug chemotherapy after mastectomy: a Cancer and Leukemia Group B (CALGB) study.

The Cancer and Leukemia Group B (CALB) has conducted a randomized study of adjuvant chemotherapy in patients with breast cancer who have involved axillary nodes at the time of mastectomy. Five-drug treatment (CMFVP) was compared with three-drug treatment (CMF). For patients with more than three involved nodes, the CMFVP regimen produced a significantly prolonged disease-free survival in comparison to the CMF regimen.

Cholesterol and obesity as prognostic factors in breast cancer.

Analysis of disease-free survival rates in 374 women with operable breast cancer revealed that preoperative weight, particularly in combination with serum cholesterol, is a significant prognostic determinant. Overall, women weighing under 150 pounds had a significantly higher cumulative five-year disease-free survival rate (67%) compared with women weighing more (49%) (z = 2.2298, P = 0.026). Women with low serum cholesterol levels had better cumulative five-year disease-free survival (67%) than women with high serum cholesterol levels (58%) (z = 1.1008, P = 0.27). The combination of high weight and high serum cholesterol levels was associated with an extremely poor cumulative five-year disease-free survival (32%) compared with that observed for women in whom values of either, or both, variables were low (68%) (z = 3.7843, P = 0.0004). These patterns in disease-free survival persisted even after controlling for tumor stage. The findings indicate that weight and cholesterol, in addition to their previously reported effect on the risk of breast cancer development, influence significantly the subsequent course of the disease.

Radioisotopic 51Cr-leukocyte adherence inhibition (LAI) assay. I. Demonstration of anti-tumor immunity in patients with breast carcinoma.

A simplified radioisotopic leukocyte adherence inhibition assay (51Cr-LAI assay) was used to determine tumor-directed immune responses in patients with cancer of the breast. Essential steps in development of this assay are the standardization of conditions for optimal 51Cr uptake by peripheral blood lymphocytes (PBL) and the inclusion of autologous or normal AB serum in the incubation media. A dextrose salt mixture (GNK) was found to enhance intracellular uptake of 51Cr significantly (8-fold) without affecting viability of the cells or without causing selective loss of lymphocyte subpopulations. The presence of 10% autologous or normal AB serum prevented non-specific LAI responses to unrelated tumor antigens. In a study of 46 preoperative patients with suspected breast cancer, clear and accurate prediction of the presence of cancer was achieved with this new assay. All patients with localized breast cancer showed significant adherence inhibition in response to allogeneic breast tumor extracts whereas normal control women and patients with benign diseases did not respond. Neither patients with cancer nor those with benign breast diseases reacted to extracts of benign breast tissue antigens. LAI reactivities appeared to be directed selectively against tumor-associated antigens (TAA) and reflect specific antitumor immunity. This short term (4 h) 51Cr-LAI assay provides reproducible and specific results analogous to those using tube-LAI assay. The test has the advantages of being accurate, sensitive and free from technical bias.

Parity and prognosis in breast cancer.

Analysis of five-year disease-free survival rates in 608 women with operable breast cancer revealed that the reproductive history is a significant prognostic determinant. Overall parous women had a significantly higher cumulative five-year disease-free survival rate (60%), compared to the nulliparous (46%) (z = 2.5, p = 0.012). Significant differences were also noted when gravidity in addition to parity was taken as the determinant. The corresponding disease-free survival rates were 61% and 50%, respectively (z = 1.98, p = 0.048). Five-year survival rates were influenced in a similar manner by these variables but the observed differences were less significant. The trend toward higher survival rates in parous and gravidae women were noted in all tumor stages but achieved statistical significance only in stage III. The findings indicate that parity and gravidity affect not only the risk of breast cancer development but also the subsequent course of the disease. Parity seems to be a strong risk and prognostic factor than gravidity.

Survival following mastectomy for stage III breast cancer.

Patients with locally advanced breast cancer have been considered unsuitable for curative surgical therapy and are usually approached with other treatment modalities. Review of the results of radical mastectomy in 228 patients with stage III breast cancer demonstrates actuarial survival of 33 per cent at five years and 22 per cent at ten years. Treatment with preoperative or postoperative radiotherapy as employed did not lead to survival superior to that of mastectomy alone. Evidence of local or regional recurrence developed in 27 per cent of patients. In 73 per cent the first recurrence was systemic. This retrospective study suggests that the prognosis for locally advanced breast cancer is not as dismal as has been previously reported. The importance of nodal involvement is again emphasized. A randomized trial of mastectomy with adjuvant chemotherapy for locally advanced breast cancer is warranted. Such a study is in progress at our institution.