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Purpose: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation., Patients and Methods: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years)., Results: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF., Conclusion: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.

Purpose: To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR)., Patients and Methods: One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy., Results: Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P < .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P=.74). Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment was always the most significant covariate in time-to-relapse models., Conclusion: There is definite toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients.

The optimal dose and schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer are not known. Based on our phase I study in non-small cell lung cancer, in which the dose intensity of paclitaxel was successfully escalated by using a weekly schedule, we initiated a phase II study of weekly paclitaxel in previously untreated patients with metastatic breast cancer (MBC) and locally advanced breast cancer (LABC). Treatment consists of weekly paclitaxel 175 mg/m2 intravenously over 3 hours for 6 weeks, followed by a 2-week break. Doses are modified for neutropenia (absolute neutrophil count < 1,500/microL), bilirubin levels greater than 1.5 times normal, or greater than grade 1 neuropathy. Patients with MBC continue treatment until disease progression. Patients with LABC receive one to two cycles before proceeding to surgery if resectable. Thus far, 15 patients, eight with MBC and seven with LABC, are assessable for response and/or toxicity. Most patients have required dose modification, with median delivery of 75% (cycle 1) and 50% (cycle 2) of the planned dose of paclitaxel. Neutropenia has been the most common cause of dose reductions, although only one patient required treatment for neutropenic fever. Six patients have developed grade 2/3 peripheral sensory neuropathy, but with dose reductions many have continued treatment with stable or improving neurologic symptoms. Objective responses have been seen in 12 of 14 assessable patients, including six with MBC (one complete response, five partial responses) and six with LABC (two complete responses, four partial responses), for an overall response rate of 86% (95% confidence interval, 66% to 96%). All responding LABC patients have been rendered free from disease at surgery. These preliminary results are very encouraging. Accrual to the study continues.

Purpose: To investigate the long-term survival of premenopausal women with previously untreated first recurrence or metastases of breast cancer entered on Eastern Cooperative Oncology Group (ECOG) study 2177 (EST 2177), which completed accrual in June 1983., Materials and Methods: One hundred forty-seven premenopausal women with metastatic breast cancer were entered onto the study. Eighty-nine patients with estrogen receptor (ER)-positive and ER-unknown disease were randomized to receive cyclophosphamide (CTX), doxorubicin (ADR), and fluorouracil (FU) (CAF) or surgical oophorectomy plus CAF (O+CAF). Fifty-eight patients with known ER-negative disease were treated with CAF. Survival time was measured from the time of study entry. Randomization was stratified by performance status (PS), dominant metastatic site, and ER status., Results: One hundred thirty patients were eligible. The median survival time of randomized patients was 35 months (90% confidence interval, 28.9 to 54.3), with 28% alive at 5 years. The overall median survival duration, including ER-negative patients, was 30 months. There was no significant difference in survival time between the randomized treatments (median, 42 months for O+CAF and 30 months for CAF). In models of survival time, age > or = 45 years and last menstruation within 1 month were associated with significantly longer survival (P < .004 for each). There were also three significant interactions with treatment (even after correction for multiple comparisons): age (P = .00009; O+CAF associated with longer survival in patients < 45 years, CAF associated with longer survival in patients > 45 years), PS (P = .002; O+CAF associated with consistently better survival in PS O patients), and disease-free interval (DFI)., Conclusion: Long-term follow-up data of premenopausal women with metastatic breast cancer show a longer than expected median survival time at 2.5 years overall and close to 5 years for patients treated with O+CAF who were ER-positive or had a good PS.

Background: Tamoxifen and aminoglutethimide are two hormone therapies reported to be effective palliative approaches for patients with metastatic breast cancer. The current trial was designed to evaluate their relative therapeutic effectiveness., Methods: Two hundred forty-nine postmenopausal women with advanced breast cancer were randomized in an Eastern Cooperative Oncology Group (ECOG) Phase III study to treatment with adrenalectomy, aminoglutethimide, or tamoxifen with crossover to alternate therapy if disease progressed. Adrenalectomy was dropped as a treatment after 2 years because of low patient accrual., Results: There were 216 evaluable patients entered in the study with 108 initially randomized to aminoglutethimide and 108 to receive tamoxifen therapy. The overall response rate for aminoglutethimide was 45%, and for tamoxifen it was 27%. One institution had a response rate of 60% with aminoglutethimide and only 4% with tamoxifen, whereas all of the other institutions combined had a response rate of 41% with aminoglutethimide and 34% with tamoxifen. Eighty-seven evaluable patients crossed over to the other drug (44 to aminoglutethimide and 43 to tamoxifen). There was a 36% response rate to aminoglutethimide and 19% to tamoxifen, with stable disease in 36% of both groups. The overall survival rates were identical. Toxicity was greater with aminoglutethimide (dermatitis) but was not life-threatening. Glucocorticoid support with either dexamethasone or hydrocortisone was acceptable., Conclusions: Both aminoglutethimide and tamoxifen produced responses in postmenopausal patients with breast cancer, and a significant number of crossover responses were observed. Of interest in this randomized study was the observation that one institution had a markedly different response rate on induction, reinforcing the need for multi-institution trials in Phase III studies.

Purpose: This study analyzes the long-term results and causes of death in elderly women with node-positive breast cancer who participated in a double-blind adjuvant trial that compared tamoxifen with placebo to determine the benefit of 2 years of treatment., Patients and Methods: One hundred eighty-one women 65 to 84 years old were given 20 mg of tamoxifen or placebo daily for 2 years after stratification by estrogen receptor status, tumor size, and degree of lymph node involvement. Approximately 30% of patients were older than 70 years and 20% were older than 75 years. Eighty-five percent were estrogen receptor-positive. Median follow-up was 10 years., Results: Among the 168 eligible patients, there have been 98 recurrences (59 placebo v 39 tamoxifen), with reduced distant and bone-only first sites in patients treated with tamoxifen. Median time to failure was 4.4 years for placebo versus 7.4 years for tamoxifen (log-rank P = .001). A similar number of new nonbreast cancers occurred in each arm (seven placebo v six tamoxifen), but a reduced number of opposite-breast cancers (five placebo v one tamoxifen) was noted. Overall, there were 102 deaths (57 placebo v 45 tamoxifen). Median survivals were 8.0 years with placebo and 8.5 years with tamoxifen (log-rank P = .063); 50% of the tamoxifen patients and 33% of the placebo patients are still alive. Sixty-one percent of the deaths were reported to have been caused by breast cancer recurrence, 4% by other cancers, and 22% by the sequelae of non-cancer-related illness, with equal distributions for cardiovascular and cerebrovascular disease. There was no increase in the number of endometrial or other types of cancer, or thrombotic or orthopedic complications in this older group., Conclusion: Tamoxifen currently is the treatment of choice for elderly women with breast cancer. It extends the time to treatment failure by 3 years and reduces the number of recurrences, deaths, distant and bone-only first recurrences, and second breast cancers.

The current trial was designed to assess whether the addition of prednisone or prednisone + tamoxifen would enhance the therapeutic effectiveness of 1 year of adjuvant CMF therapy. Premenopausal women with ipsilateral axillary node-positive breast carcinoma and known estrogen receptor (ER) status were randomized to receive 1 year of postoperative treatment with 12 28-day cycles of cyclophosphamide, methotrexate, 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). There were 553 analyzed cases with 188 receiving CMF, 183 CMFP, and 182 CMFPT. The overall time to relapse (TTR) and survival comparisons between the regimens are not statistically different at a median follow-up time of 7.7 years. The major subgroups currently with a suggestive TTR difference are greater than 3N+ (CMFPT greater than CMF, P = 0.07) and estrogen receptor-negative (ER-) greater than 3N+ (CMFPT greater than CMF, P = 0.03). Patients receiving CMFPT appeared to have a superior survival to CMF in the ER- greater than 3N+ cohort (P = 0.02). The following patient characteristics were associated with a significantly longer TTR: decreasing nodal involvement or tumor size, positive ER status, age greater than or equal to 40 years, and decreasing obesity. The favorable effects of decreasing nodal involvement, positive ER status, age 40 years or greater, and decreasing obesity carried over to survival. Development of amenorrhea was also significantly associated with improved survival (P = 0.001). Toxicity was increased by the addition of prednisone to CMF and by the addition of tamoxifen to CMFP. Overall relapse patterns were similar among the three regimens. The results of the current trial do not currently suggest an overall therapeutic benefit for adding prednisone or only 1 year of tamoxifen to CMF adjuvant treatment.

Two human breast carcinoma cell lines, EP and MW, were established in culture from malignant pleural effusions. In addition to producing tumors in antithymocyte serum-immunosuppressed mice, both cell lines showed epithelial characteristics and anchorage-independent growth in soft agar. EP and MW differed in morphology (spindle-shaped versus round), chromosomal mode (hyperdiploid versus near triploid), estrogen receptor content (43.8 versus 5.1 fmol/mg protein), cloning efficiency (0.24 versus 15%), and activities (milliunits/10(6) cells) of creatine phosphokinase (25.7 versus 62.6) and lactate dehydrogenase (346.7 versus 778.5). Electron microscopy revealed that MW cells had more perinuclear filamentous material and more frequent intracytoplasmic vacuole formation than did EP cells. While having no effect on MW cells at the concentrations studied (10(-5) to 10(-11) M), beta-estradiol (10(-7) M) stimulated the growth of EP cells by 106% over the hormone-depleted control. In a variety of systems, EP was consistently the more drug sensitive of the two lines. In vitro, EP was significantly (p less than 0.001) more sensitive to methotrexate, vincristine, and 5-fluorouracil, respectively. In antithymocyte serum-mouse xenografts, EP displayed a greater response to three different dosages of a combination of cyclophosphamide, methotrexate, and 5-fluorouracil. One such dosage (cyclophosphamide, 32.0 mg/kg/day; methotrexate, 13.0 mg/kg/day; 5-fluorouracil, 190.0 mg/kg/day; for 1 day) reduced EP and MW tumor weights to 5.9 and 41% of controls, respectively. These results correlated well with the clinical responses.

A total of 202 patients with advanced breast cancer were entered into two prospectively randomized Phase II trials conducted by the Eastern Cooperative Oncology Group, in an effort to identify promising agents and combinations for previously treated cases. Patients in Study 1 received bleomycin, CCNU, or streptozotocin and those in Study 2 received tilorone, Baker's antifol, or a combination of 5-fluorodeoxyuridine plus arabinosyl cytosine. Partial responses were seen only with bleomycin, Baker's antifol, and 5-fluorodeoxyuridine plus arabinosyl cytosine. The median times to treatment failure ranged from 3.6 weeks to 5.7 weeks, and the median survival times, from 8 weeks to 25 weeks for tilorone and bleomycin, respectively. Toxic reactions was primarily hematologic and gastrointestinal, but skin, neurologic, respiratory, and renal abnormalities were noted in some treatment arms. The treatment schedules outlined and the toxic effects noted provide background information that might prove useful in designing complex new chemotherapeutic programs, since there is pharmacological rationale for incorporating some of the agents tested into present standard combination chemotherapy regimens.

In a randomized crossover study, 181 patients over the age of 65 with recurrent breast cancer received either tamoxifen or cyclophosphamide, methotrexate, and fluorouracil (CMF). After progression on tamoxifen, a hormone withdrawal period was required. Because of altered pharmacokinetics with aging, creatinine clearance was used in calculating the dose of CMF. Response rates were 45% on tamoxifen and 38% on CMF, with median durations of 10.4 and 7.9 months, respectively. Survival rates tended to favor tamoxifen as the initial treatment even in estrogen-receptor-negative patients. Additional disease control with hormone withdrawal occurred in 23% of patients, and this benefit was highly correlated with prior hormone response. We conclude that initiation of hormone therapy rather than CMF chemotherapy is justified in almost all situations in elderly patients, and combination chemotherapy, is safe and useful after hormone failure if modified on the basis of renal dysfunction.

A total of 268 patients with metastatic breast cancer were prospectively randomized to receive Adriamycin-vincristine (AV) alone, AV plus dibromodulcitol (AVD), or AV plus ICRF-159 (AVI). Two hundred thirty were eligible and had received prior chemotherapy. The objective response rates were 27%, 23%, and 16% for AV, AVD and AVI, respectively, and an additional 44% had stabilization of disease. Duration of responses ranged from 4.1 to 4.6 months and the times to treatment failure from 2.9 to 3.8 months. Median survivals ranged from 7.1 to 8.3 months. Performance status and the presence of liver or brain metastases were significant prognostic variables for outcome. These studies show that AVI is inferior to AV with respect to survival when prognostic variables are taken into account in a multivariate model, whereas AVD which utilizes a lower dose of Adriamycin appears to have comparable antitumor activity to AV. This does not appear to offer any benefit to patients previously treated with chemotherapy, as in this trial, but it may be an advantage to previously untreated patients since Adriamycin can be administered to responding patients over a longer period of time before an unacceptable total cumulative dose is reached.

We examined the relationship between age and extent of disease at initial diagnosis as part of a population-based, prospective study documenting the patterns of care received by over 1500 newly diagnosed lung, breast, and colorectal cancer patients identified in nine Rhode Island hospitals. For each cancer site examined, no age by extent of disease relationship was observed; however, analysis by sex among lung cancer patients indicated an inverse age relationship for men. The absence of an age effect for breast cancer patients is in contrast to earlier research findings that identify a positive association between extent of disease and age at diagnosis. Past results may reflect age-related differences in patient and physician screening behavior characteristic of earlier time periods.

The Eastern Cooperative Oncology Group (ECOG) trial of adjuvant cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen (CMFPT) for 1 year compared with observation alone in 265 postmenopausal patients with node-positive breast cancer is reported with 74 months median follow-up. Overall relapse-free survival tended to favor CMFPT (P = .08), but no survival differences existed between any treatment group. The addition of tamoxifen to CMFP led to slightly (but not significantly) better relapse-free status in all subgroups analyzed. Subgroup analysis based on stratification variables showed significant benefit from CMFP (+/- T) only in estrogen receptor (ER)-negative patients with respect to disease-free status (P = .0003), but not survival (P = .54). Relapse-free status was actually worse for CMFP-treated patients with ER-positive tumors, but not significantly so (P = .15). By multivariate analysis other significant risk factors for relapse-free status were primary tumor size, number of nodes pathologically involved, and the number of nodes examined. ER status was prognostic only for the observation group with the benefit from chemotherapy on ER-negative patients obliterating this difference in treated patients. Survival was affected by the number of involved nodes, tumor size, presence of tumor necrosis, and patient obesity. Analysis of toxicity showed elevation of liver enzymes during the first year to be more common in the observation group compared with those patients receiving adjuvant treatment and to be associated with early recurrence. Toxicity from adjuvant treatment persisted beyond termination of therapy in 53% of patients, but was usually mild and self-limited. We conclude CMFPT offers relapse-free survival benefit in ER-negative patients, but the value of chemotherapy in ER-positive postmenopausal, node-positive patients must be questioned.

One hundred fifty-five eligible women with metastatic breast cancer were randomly allocated to receive monthly cycles of either CMFP (cyclophosphamide, methotrexate, 5-fluorouracil, prednisone) or CAF (cyclophosphamide, doxorubicin, 5-fluorouracil), and 12 patients were studied to evaluate the effects of additional Corynebacterium parvum immunotherapy. Overall response rates of 53% were seen with CMFP and CAF. CAF was associated with significantly more complete responses than CMFP (17% v 5%). However, CAF therapy was administered for eight months and CMFP for six months. Only 13% of the CAF patients had a complete response during the first six months of chemotherapy, and this was not significantly different from the complete response rate on CMFP. The median response durations (CMFP, 6.3 months; CAF, 11.0 months), times to treatment failure (CMFP, 5.7 months; CAF, 7.8 months), and survival times (CMFP, 15.8 months; CAF, 18.6 months) were not statistically different. Other investigators who have compared CAF to CMF-containing regimens have reported a large advantage in CAF therapy among patients with "good risk" sites of metastases (local-regional recurrence, bone, lung nodules). Such a finding was not confirmed by our study: in multivariate analyses the groups associated with an advantage for CAF tended to have a poorer prognosis than the groups associated with an advantage for CMFP. There was significantly more nausea and vomiting after CAF treatment, and CMFP treatment was associated with significantly more edema, Cushingoid features, fever, and eye symptoms.

Data on 162 women (90 premenopausal and 72 postmenopausal) with metastatic breast cancer randomized to receive cyclophosphamide, Adriamycin (doxorubicin) and 5-fluorouracil (CAF) on two Eastern Cooperative Oncology Group (ECOG) protocols were analyzed. Twenty-three percent had complete remission; 39% had partial remission; 28% had no change; and 3% had disease progression. Of those patients in whom receptors were known, response rates were 65% for estrogen (ER)-receptor positive and 70% for ER-negative patients. The median duration of response was 11.4 months. The median survival time from the start of CAF was 20.2 months. The response rate, time to treatment failure (TTF), and median survival time were superior in the premenopausal women. These differences ceased, however, to be statistically significant in logistic models. Factors significantly associated with longer TTF and longer survival were as follows: one or two organs with metastases (TTF, P less than 0.0001; survival, P less than 0.0001); dominant site other than soft tissue (TTF, P less than 0.0001; survival, P = 0.05); and an initial good performance status (TTF, P = 0.007; survival, P = 0.02). Patients with ER-positive disease had a significantly longer median survival time (P = 0.003).

One hundred eighty-one elderly women with stage II breast cancer were prospectively randomized to receive tamoxifen or placebo for 24 months in a double-blind adjuvant trial conducted by the Eastern Cooperative Oncology Group. They were stratified prior to randomization on the basis of the number of positive axillary nodes and the estrogen receptor status of their primary tumor. One hundred seventy were considered eligible and analyzed in this trial. The median age was 71 years with a range from 65 to 84 years. Twenty-one percent of the patients were over the age of 75 and 33% were between 71 and 75 years. Estrogen receptor status was positive in 85% of the patients and unknown in another 12%. Progesterone receptor status was positive in 35%, negative in 16%, and unknown in 49%. With a median follow-up of 55 months, the overall percent disease free at 4 years is 73 for the tamoxifen arm and 52 for the placebo arm (P = .003). Significant benefit is seen following tamoxifen in the subsets with 4-10 positive axillary lymph nodes, those who were estrogen receptor positive, or progesterone receptor unknown, and those who had a tumor size less than 3 cm. Most other subsets benefited as well. There were more distant (29 vs. 13) and bone only (15 vs. 3) sites of first recurrence in the placebo arm, whereas locoregional recurrences were similar (8 each). The recorded toxicity was similar, except for more hot flashes observed among women in the tamoxifen arm.(ABSTRACT TRUNCATED AT 250 WORDS)

A cell line was established from a portion of a 25-cm stromal sarcoma of the left breast of a 65-year-old woman. The clinical course was rapid with tumor recurrence on the chest wall less than 1 month after mastectomy. Other cutaneous and abdominal metastases occurred shortly thereafter, and death followed within 3 months despite chemotherapy. The cultured cells, designated RW-972, produced large amounts of acid mucopolysaccharides (hyaluronic acid) and mimicked the aggressive growth characteristics seen in the patient. After injection into nude mice, the tumor grew rapidly and occasionally produced metastases. This unique cell line, RW-972, presumably derived from the stromal component of a human malignant cystosarcoma phyllodes, might be useful in studies of experimental therapy of this rare tumor type and of lobular stromal cells of breast. It may also be used to investigate hyaluronic acid production by tumor cells.

One hundred seventy elderly women with stage II breast cancer, stratified on the basis of the number of positive axillary nodes and estrogen receptor status, were randomly assigned to receive tamoxifen or placebo for 24 months in a prospective, double-blind, adjuvant trial. The median age was 71 years with a range from 65 to 84 years. The overall percentage of patients disease-free at 4 years was 76% for those given tamoxifen and 52% for those given placebo (p = 0.0004). Benefit was seen in all subgroups of patients treated with tamoxifen. Two years of tamoxifen therapy represents an effective postoperative adjuvant treatment for elderly women with stage II breast cancer, resulting in improved time to relapse, statistically fewer distant first recurrences, and minimal toxicity. No improvement in overall survival has been seen yet.

After mastectomy, 265 postmenopausal patients with node-positive breast cancer were stratified according to pathologic nodal status and estrogen-receptor (ER) status and randomized to receive either 12 cycles of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP), or CMFP plus tamoxifen (CMFPT), or observation alone. Patients entered the study between March 1978 and July 1981. Cox regression analysis indicated that, compared to observation alone, chemotherapy (CMFP and CMFPT groups combined) led to a significant reduction in relapses by the end of the first year of study in every examined prognostic subgroup. However, after the first year the relapse-free survival curves of all treatment groups tended to merge, so that by three years 52% of the observation group and 51% of the chemotherapy groups remained disease free. Chemotherapy continued to show a significantly superior relapse-free survival rate for three years only in the subgroup of patients with ER-negative tumors (the subgroup with the largest relapse-free survival advantage at one year). The addition of tamoxifen produced no benefit or harm in any prognostic subcategory examined. ER status was prognostically important for predicting early relapse only in those patients not receiving chemotherapy, due to the greater effectiveness of this chemotherapy to prevent early relapse in the ER-negative subgroup. Treatment has had no early effect on survival. As breast cancer continues to recur even after ten or more years, later relapse patterns may alter these results.

Separate trials for premenopausal and postmenopausal (less than or equal to 65 yr of age) patients with node-positive breast carcinoma were initiated by the Eastern Cooperative Oncology Group in 1978 to evaluate adjuvant chemotherapy and chemohormonal therapy approaches. Postoperative patients were stratified by degree of axillary nodal involvement and estrogen receptor (ER) status prior to randomization. Premenopausal patients received 12 monthly cycles of intermittent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus continuous tamoxifen (CMFPT). Postmenopausal patients received either observation or 12 monthly cycles of CMFPT or CMFP. The median follow-up for the analyzed patients is 54 months for the 553 premenopausal patients and 59 months for the 223 postmenopausal patients. The premenopausal trial has not demonstrated any significant differences between the regimens for either relapse-free or overall survival. The relapse-free survival in the postmenopausal trial has demonstrated a trend for CMFPT over observation (P = .07). Both CMFP and CMFPT are associated with an improved relapse-free survival over observation alone in ER-negative patients (P = .01) and in progesterone receptor-negative patients (P = .01). However, the relapse-free survival advantages have not translated to survival. Side effects were significantly increased with the addition of P to CMF in the premenopausal trial. The addition of T to CMFP was associated with an increased incidence of edema and hot flashes in premenopausal patients; however, the latter was decreased in postmenopausal patients relative to CMFP.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred thirty-one premenopausal women with metastatic breast cancer who had received no prior systemic treatment for metastases were entered on study. Patients without prior chemotherapy with estrogen receptor (ER)-positive and ER-unknown disease were randomized to receive cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH), and 5-fluorouracil (CAF) or surgical oophorectomy followed directly by CAF (O + CAF). ER-negative patients without prior chemotherapy were directly assigned to treatment with CAF. Among randomized patients 83% have responded, and 37% have achieved a complete remission. Among ER-negative patients the complete response rate was 38%, and the complete plus partial response rate was 70%. Characteristics significantly associated with a longer time to treatment failure were age 45 or over, one or two organ sites, and performance status O. The median survival time of ER-positive patients treated with CAF is 29 months, and with O + CAF it has not yet been reached, whereas for ER-unknown patients the equivalent survival times are 41 months and 43 months respectively. For ER-negative patients treated with CAF the median survival time is 17 months. Characteristics associated with significantly longer survival among randomized patients were age 35 or over (P = .009) and only one or two organ sites involved (P = .02). Neither treatment (P = .33) nor ER status (P = .70) was significant.

Increases in cancer incidence and mortality reflect the larger numbers of elderly in the population. Using a mortality sample of 1891 biopsy-confirmed cancer patients, analyses reveal older breast, prostate, and cervical-uterine cancer victims were more likely to be diagnosed with metastases. Logistic regression analyses of subsamples of breast (N = 224), lung (N = 513), and colorectal (N = 299) cancer patients indicate that age is significantly inversely related to receipt of both subsequent chemotherapy and radiation therapy, controlling for stage of disease and presence of co-morbid disease. Exceptions to this relationship are the use of radiation therapy among nonmetastatic lung cancer patients and all breast cancer patients. The implications of these findings for current cancer control programs are discussed.