Long-term survival following relapse after 5-FU but not CMF adjuvant breast cancer therapy

Abstract

Beginning in 1974, patients with greater than or equal to 4 nodes positive following mastectomy were randomized to receive either 5-FU i.v. weekly or CMF i.v. every 2 weeks, both given for 12 months. Median follow-up now exceeds 112 months with nine year results below: (table; see text) Early results based on relapse-free survival favored CMF, but more patients currently are alive on the 5-FU arm. As the survival curves cross at 40 months, the 20% survival advantage for 5-FU did not achieve statistical significance. For 34% of patients failing adjuvant 5-FU, use of combination chemotherapy after relapse (commonly with CMFVP or CMF) resulted in long term survival. In contrast, long-term survival for patients failing adjuvant CMF was unusual. Relapse was detected while under weekly observation in a greater proportion of patients on 5-FU (36%) compared to CMF (6%) adjuvant treatment (p less than 0.05), potentially influencing tumor burden at recurrence. Hormonal therapy or radiation therapy as initial therapy after relapse was ineffective, with no long term survivors resulting on either arm. Weight increase on adjuvant chemotherapy was commonly seen, with weight increase greater than 10 kg associated with a poor prognosis. We conclude that initial improvement in relapse-free survival may not predict long term survival in adjuvant breast cancer trials since both the specific adjuvant therapy given pre-relapse as well as the type of salvage therapy given post-relapse may influence ultimate patient outcome.

Variations in the body mass index in Brazilian women undergoing adjuvant chemotherapy for breast cancer

“…In addition to adjuvant therapy, be it CTx, hormone therapy, or immunotherapy with trastuzumab-type monoclonal antibodies, metabolic and endocrine factors related to an increase in weight gain after cancer diagnosis are strongly associated with higher risk of recurrence and reduction in survival rates 14,29,[36][37][38] .…”

Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer

“…The literature regarding post-diagnosis weight gain and prognosis [18][19][20][21][22][23][24] is not extensive and it is difficult to compare results across studies, because the studies often used different measures to evaluate prognosis. Some examined only overall survival, while others use disease-free, relapsefree or recurrence-free survival, and even among the latter three, definitions often vary across study.…”

“…Differences in the definition of recurrence endpoints between studies may account for our differing results. -14 -Of the remaining six studies on weight gain and prognosis [18][19][20][21][22][23], three reported no relationship [19;20;23], and none of the three that found a negative impact on prognosis [18;21;22], reported a statistically significant effect on recurrence or any outcome measure that included only breast cancer events. A study by Camoriano et al [18] of 545 node-positive women reported a significant effect of weight gain on overall survival, but not on recurrence; and only for premenopausal, but not post-menopausal, women.…”

“…A study by Camoriano et al [18] of 545 node-positive women reported a significant effect of weight gain on overall survival, but not on recurrence; and only for premenopausal, but not post-menopausal, women. The remaining two studies had sample sizes of less than 65 and reported a relationship with overall survival [22] or disease-free survival (without defining which events were included) [21]. In addition, all of these studies [18][19][20][21][22][23] were conducted about 20 years ago when chemotherapy regimens both lasted 1 year and were frequently supplemented with steroids and early weight gains were considerably larger than has been observed in more recent studies where chemotherapy regimens are of shorter duration and are often accompanied by effective adjuvant anti-estrogen therapies.…”

“…The few studies that have addressed this issue have generally had small numbers of women, have not used the same prognostic outcomes measures and have reported inconsistent results [18][19][20][21][22][23]. The largest study to date was from the Nurse's Health Study Cohort (NHS), in which self-reported body weight measures were obtained in a subsample of over 5000 generally healthy women who were subsequently diagnosed with breast cancer and followed for a median of 9 years.…”