Role of adjuvant endocrine therapy in early-stage breast cancer

The value of adjuvant endocrine therapy in saving lives of women with estrogen receptor-positive (ER(+)) early-stage breast cancer cannot be disputed. Tamoxifen has proven to be effective in improving relapse-free and overall survival in both pre- and postmenopausal women with ER(+) early-stage breast cancer. In the meta-analysis of the Early Breast Cancer Trialists' Collaborative Group, the proportional reduction in recurrence and mortality for 5 years of tamoxifen therapy was 50% and 28% respectively for patients with ER(+) tumors. These reductions in recurrence and mortality were similar in both lymph node-negative (N(-)) and lymph node-positive (N(+)) patients and translate to an absolute improvement in 10-year survival of approximately 11% in N(+) patients and 6% in N(-) patients. Current data suggest that about 5 years of tamoxifen therapy is the optimal duration of treatment. For women with ER(-)/progesterone receptor-negative (PR(-)) tumors, tamoxifen does not lower the risk of distant metastases or improve survival. In ER(+) patients, the addition of tamoxifen to chemotherapy further lowers the risk of recurrence by about 30% to 40% when compared to chemotherapy alone. In premenopausal women with ER(+) breast cancer, ovarian ablation has proven to be as effective as chemotherapy in improving both relapse-free and overall survival and the potential additive role of ovarian ablation to chemotherapy and/or tamoxifen is presently being explored in clinical trials. The combination of tamoxifen and ovarian ablation is currently being tested and may be superior to tamoxifen alone. In addition, newer, more effective, and less toxic aromatase inhibitors are also being evaluated in clinical trials in the adjuvant setting and have great promise. "Pure" antiestrogens or selective estrogen receptor down-regulators (SERDs) will be studied in adjuvant clinical trials in the near future. Recent data also suggest that molecular markers such as HER-2/neu may predict the response to endocrine therapy, and other predictive factors are currently being evaluated. Lastly, there is renewed interest in neoadjuvant endocrine therapy, a treatment option that may select those patients with early-stage breast cancer most likely to benefit from endocrine therapy.     

p53 accumulation is a strong predictor of recurrence in estrogen receptor‐positive breast cancer patients treated with aromatase inhibitors

Aromatase inhibitors have played a central role in endocrine therapy for estrogen receptor (ER)‐positive breast cancer in postmenopausal women. However, factors predictive of the efficacy of aromatase inhibitors, and prognostic factors, both for early and late recurrence in women treated with adjuvant aromatase inhibitors have not been identified. Whole genome analysis identified that a TP53 gene mutation exists in ER‐positive breast cancers, although the frequency of TP53 gene mutation in luminal tumors is lower compared with basal‐like or human epidermal growth factor receptor type 2 (HER2)‐positive breast cancers. We examined expression of p53, as well as ER, progesterone receptor, HER2 and Ki‐67 using immunohistochemistry in postmenopausal ER‐positive breast cancer patients who were treated with aromatase inhibitors as adjuvant endocrine therapy. There were 53 (21%) tumors that contained 10% or more p53‐positive cells. High p53 expression was positively correlated with tumor grade, HER2 score and Ki‐67 expression. Significant association was observed between disease‐free survival and high p53 expression in multivariate analysis (P < 0.0001). Compared with women without recurrence, women with early recurrence had significantly higher p53 expression (P < 0.0001), as did women with late recurrence (P = 0.037). The present study demonstrates that p53 accumulation is a strong predictor of both early and late recurrence in ER‐positive breast cancer patients treated with aromatase inhibitors as adjuvant endocrine therapy. TP53 gene alteration might be a key biological characteristic of ER‐positive breast cancer.     

Post-relapse survival in patients with the early and late distant recurrence in estrogen receptor-positive HER2-negative breast cancer

Background

Few studies have been performed on post-relapse survival in patients with the early and late distant recurrence in estrogen receptor (ER)-positive, HER2-negative breast cancer.

Methods

A total of 205 patients with the early distant recurrence and 134 patients with the late distant recurrence of ER-positive, HER2-negative breast cancer who had undergone breast surgery or neoadjuvant chemotherapy between January 2000 and December 2004 were registered from nine institutions. Prognostic factors for post-relapse survival in patients with the early and late recurrence were analyzed.

Results

Post-relapse survival was significantly longer in patients with the late recurrence than in patients with the early recurrence. Predictive factors for post-relapse survival in patients with the early recurrence were lack of adjuvant chemotherapy, a long disease-free interval, and long durations of endocrine therapies and chemotherapies after relapse. In patients with the late recurrence, post-relapse survival was significantly improved for those individuals with one metastatic organ at relapse and individuals who were treated with the first-line and subsequent endocrine therapies for prolonged periods. Moreover, ER expression in primary breast tumors of late recurrence patients was significantly higher with a duration of the first-line endocrine therapy >6 months than in those with a duration ≤6 months.

Conclusion

Predictors for prognosis after relapse differed between patients with the early and late distant recurrence. Endocrine responsiveness after relapse is a key factor for improved post-relapse survival, and it is thus important to establish whether metastatic tumors are endocrine-resistant in ER-positive, HER2-negative recurrent breast cancer.

     

The Stockholm trial on adjuvant tamoxifen in early breast cancer

Summary The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P<0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P<0.01) and deaths by 7% (P>0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.     

Significance of estrogen and progesterone receptors, disease-free interval, and site of first metastasis on survival of breast cancer patients

Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease-free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment.     

ER(-)PR(+)乳腺癌辅助内分泌治疗的疗效

背景与目的：孕激素受体（PR）状态是雌激素受体（ER）状态预测乳腺癌辅助内分泌治疗的补充，临床上推荐ER阳性（＋）或PR（＋）患者均可接受内分泌治疗。ER阴性（-）PR（＋）肿瘤应用辅助内分泌治疗的疗效如何还存在争议。本研究将探讨辅助内分泌治疗对ER（＋）PR（＋）与ER（-）PR（＋）乳腺癌的疗效，并研究ER（-）PR（＋）患者的临床病理特性及预后。方法：回顾了1991年1月-2001年12月间的1863位ER／PR资料可用的可手术乳腺癌患者资料，ER、PR均采用免疫组化法检测。中位随访48个月，比较ER（-）PR（＋）组（205例）和ER（＋）PR（＋）组（798例）接受或不接受辅助内分泌治疗（3～5年的他莫昔芬）的无病生存（DFS）和总生存（0s）的差异。结果：ER（-）PR（＋）患者占全部乳腺癌患者的11．0％，中位年龄49岁，肿块中值大小3．0cm，其中未绝经者比例高达63．9％。ER（-）PR（＋）组较ER（＋）PR（＋）组而言，腋淋巴结转移数高、肿块大、分期晚。ER（＋）PR（＋）组和ER（-）PR（＋）组未行内分泌治疗时，组间生存差异无显著性；内分泌治疗后，两组的生存率均有所提高，但ER（＋）PR（＋）组的预后比ER（-）PR（＋）组更好（DFS：P=0．016，OS：P=0．007）。多因素分析显示对ER（-）PR（＋）患者，仅有腋淋巴结状态是独立的预后指标。结论：辅助内分泌治疗对ER（＋）PR（＋）乳腺癌的疗效优于对ER（-）PR（＋）乳腺癌的疗效，ER（-）PR（＋）患者能从内分泌治疗中得到一定收益，但较有限。     

Six-year results of the Eastern Cooperative Oncology Group trial of observation versus CMFP versus CMFPT in postmenopausal patients with node-positive breast cancer

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.     

T1N0M0乳腺癌的激素受体状况对预后的影响

对４８例Ｔ１Ｎ０Ｍ０乳腺癌患者进行激素受体与预后关系的分析，平均随诊时间为８．５年，全部病例行改良根治术，术后均未进行辅助治疗。雌激素受体或孕酮受体阳性组病例的无复发，生存率明显优于相应之阴性组病例。初步认为Ｔ１Ｎ０Ｍ０浸润性乳腺癌病例的雌激素及／或孕酮受体阴性者应进行术后化疗。     

Five or more years of adjuvant endocrine therapy in breast cancer: a meta-analysis of published randomised trials

Five years of adjuvant hormonal therapy is the standard of care in early breast cancer (BC) expressing oestrogen receptors (ER+). Prolonged duration of adjuvant endocrine therapy is implemented to prevent recurrence and death; in particular, its carryover effect may prevent very late events. This meta-analysis compares the efficacy of 5 years of hormonal therapy alone with that of additional years of hormonal therapy, in patients with early BC. Randomised trials comparing 5 years versus more than 5 years of hormonal therapy in BC were identified by electronic searches of PubMed, EMBASE, ISI Web of Science and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using the fixed- or random-effects models. The primary endpoints were overall survival (OS), BC-specific survival (BCSS) and relapse-free survival (RFS) reported as odds ratios (ORs) and 95 % confidence interval (CI). Eight trials, including 29,138 patients, were identified. Overall, in ER+ BCs, extended endocrine therapy beyond 5 years of tamoxifen significantly improved OS (OR, 0.89; 95 % CI 0.80–0.99; P = 0.03), BCSS (OR, 0.78; 95 % CI 0.69–0.9; P = 0.0003) and RFS (OR 0.72; 95 % CI 0.56–0.92; P = 0.01) compared with 5 years of hormonal therapy alone. Loco-regional and distant relapses were reduced by 36 and 13 %, respectively. Compared with 5 years of tamoxifen, additional adjuvant endocrine therapy reduced risk of death and relapse of ER+ BC by ~10 and 30 %, respectively. This strategy should be considered in patients free of disease after 5 years of hormonal therapy.     

Endocrine sensitivity of estrogen receptor‐positive breast cancer is negatively correlated with aspartate‐β‐hydroxylase expression

Although prognostic markers for early estrogen receptor (ER)‐positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER‐positive breast cancer cells was correlated with the expression of aspartate‐β‐hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER‐positive and tamoxifen‐resistant breast cancer cells was upregulated by the MAPK and phosphoinositide‐3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance. In the clinical setting, ASPH expression was negatively correlated with recurrence‐free survival of luminal B breast cancer patients that received adjuvant endocrine therapy, but not in patients that did not receive adjuvant endocrine therapy. Luminal B breast cancer is one of the intrinsic molecular subtypes identified by the Prediction Analysis of Microarray 50 (PAM50) multiple gene classifier, and because of its poor response to endocrine therapy, chemotherapy in addition to endocrine therapy is generally required after surgical resection. Our results suggest that the endocrine sensitivity of luminal B breast cancer can be assessed by examining ASPH expression, which promotes the consideration of a prospective study on the association between ASPH expression at the mRNA and protein levels in luminal B breast cancer and subsequent response to endocrine therapy.     

The influence of hormone receptors and hormonal adjuvant therapy on disease-free survival in breast cancer: a multifactorial analysis

The prognostic value of estrogen (ER) and progesterone (PgR) receptor status and the influence of hormonal adjuvant therapy on disease-free survival (DFS) in breast cancer were evaluated in 680 women after radical and modified radical mastectomy. The effect of 17 variables, including clinical data, TNM, hormone receptor status, histology and adjuvant therapy, on the DFS observed was analyzed, using a multivariate proportional hazard model. Multifactorial analysis revealed that DFS was strongly related to the number of positive axillary nodes (P < 0.001) and the histological grade of the tumor (P = 0.05). Moreover, the DFS of ER-positive patients with node involvement was significantly improved by hormonal adjuvant therapy (tamoxifen). Combination of adjuvant chemotherapy with hormonal therapy did not enhance its effectiveness. Recurrence rates of either node-negative or ER-negative patients were not affected by either adjuvant therapy. When no systemic therapy was given, no significant relationship between ER or PgR content of the tumor and the DFS was observed. These findings suggest that hormone receptor status is not an independent prognostic factor but provides reliable information on responsiveness to adjuvant hormonal therapy which is very effective in patients selected on the basis of ER assay.     

Estrogen-receptor status and response to chemotherapy in early and advanced breast cancer

Summary The value of estrogen receptor (ER) status in the prediction of tumor response to combination chemotherapy was retrospectively analyzed in breast cancer patients selected for prospective controlled trials of chemotherapy (85 with advanced disease and 256 with operable tumors). All patients were previously untreated with either chemotherapy or endocrine therapy, and in all instances drug therapy was applied at the time of primary treatment. The ER status was considered positive in 54% of women with advanced disease and in 70% of women with operable breast tumor and positive axillary nodes, respectively. About 12% of patients were considered to have borderline ER. The response to drug therapy (complete plus partial remission in advanced breast cancer and 3-year relapse-free survival after mastectomy, respectively) was not significantly different between ER+ and ER—tumors. The comparative results of ER+ vs ER—patients were similar whether the cutoff point for ER+ tumors was >5 or >10 fmol/mg cytosol protein. The present results indicate that in advanced and early breast cancer combination chemotherapy is effective regardless of ER status. Therefore, in the presence of ER+ tumors there is no reason to delay the early administration of effective chemotherapy. This is particularly true both in the presence of rapidly progressing metastatic disease and in the adjuvant setting.Presented in part at the 15th Annual Meeting of the American Society of Clinical Oncology (New Orleans, May 14–15, 1979)     

Results of treating stage III carcinoma of the breast by primary radiation therapy.

One hundred sixteen patients with stage III carcinoma of the breast were treated by primary radiation therapy. The 5-year actuarial survival and relapse-free survival were 25% and 22%, respectively. The 5-year actuarial probability of local tumor control for the entire group was 64%. In patients undergoing an excisional biopsy and an interstitial implant of the primary tumor area, local control was 100%. In patients who had either an excisional biopsy or an implant, the 5-year actuarial probability of local control was 77% and 76%, respectively. In contrast, in patients having neither an excisional biopsy nor an implant, local control was only 41%. In patients receiving a total dose of greater than 6000 rad, from external beam treatment or from external beam plus an interstitial implant, the local control was 78% compared to 39% in patients receiving a total dose of less than 6000 rad. Forty-one patients received some form of adjuvant therapy. Both local control and relapse-free survival were improved in patients receiving chemotherapy as the sole adjuvant and in patients receiving chemotherapy combined with an endocrine ablative procedure. However, patients treated with only an endocrine ablative procedure had no improvement in survival nor in local control. These results indicate that primary radiation therapy can provide local control in a high proportion of patients with stage III carcinoma of the breast and suggest that chemotherapy is effective in improving both local control and survival in these patients.     

78例乳腺癌改良根治术后pT3N0M0期患者放疗价值探讨

目的 探讨乳腺癌改良根治术后病理分期为T₃N₀期患者的术后放疗价值。方法 回顾分析1997-2014年收治的乳腺癌改良根治术后患者资料,筛选标准为女性、术后病理提示浸润性癌、肿瘤最大径>5 cm且腋窝淋巴结未见转移、未接受新辅助化疗及内分泌治疗,且无远处转移及其他第二原发癌。78例符合条件。40例(51%)接受术后放疗,67例(86%)接受辅助化疗。Kaplan-Meier法计算DFS、OS及LRR率,组间差异用Logrank法检验。结果 中位随访时间79个月(6~232个月),5年OS、DFS和LRR分别为89%、87%和2%。放疗组与未放疗组患者5年DFS分别为84%与91%(P=0.641),5年OS分别为84%与96%(P=0.126),5年LRR分别为0%和5%。仅ER/PR状态、分子分型影响患者DFS (P=0.002、0.031)。未放疗组有1例患者出现胸壁复发。结论 乳腺癌改良根治术后T₃N₀M₀期患者LRR率较低,仅ER/PR状态及分子分型影响患者DFS。在有效系统全身治疗基础上术后病理T₃N₀患者可能不需全部接受胸壁+锁骨上野放疗,但仍需大样本病例证实。     

Prognostic and predictive value of epidermal growth factor receptor in recurrent breast cancer.

PURPOSE: The prognostic and predictive value of epidermal growth factor receptor (EGFR) expression was evaluated in patients with recurrent breast cancer. EXPERIMENTAL DESIGN: The immunohistochemical expression of EGFR was analyzed in 241 patients with recurrent breast cancer. RESULTS: EGFR expression was positive in 87 of 241 (36%) patients with recurrent breast cancer, whereas the EGFR expression inversely correlated with the estrogen receptor (ER) status. The patients with positive EGFR expression had a significantly worse postrelapse survival than those with a negative EGFR expression, whereas EGFR expression also had a postrelapse prognostic significance in patients with a positive ER status. A multivariate analysis indicated EGFR expression to be an independently significant factor for postrelapse survival, whereas a multivariate analysis in which the ER status was added to variables indicated that ER status but not EGFR expression to be an independently significant factor. There was a significant difference between positive and negative EGFR expression in the treatment response of 82 patients who received hormonal therapies and 374 patients who received chemotherapies, whereas a multivariate analysis indicated the responses to the first-line treatment and EGFR expression to be independently significant factors for postrelapse survival. CONCLUSIONS: EGFR expression had prognostic significance in recurrent breast cancer, whereas its prognostic value was not independent of the ER status. In addition, the EGFR expression was suggested to be related to the responses to hormonal therapy and chemotherapy, whereas the EGFR expression had an additional prognostic value that was independent of the treatment response.     

369例ER阳性乳腺癌辅助内分泌治疗的前瞻性临床研究

目的 评价ER阳性乳癌根治术后辅助内分泌治疗的效果。方法 ER阳性的根治性术后乳腺癌患者分为内分泌治疗及化疗两组,进行全身辅助治疗。内分泌治疗组194例,服用三苯氧胺（TAM）5年,其中绝经前患者均先切除双侧卵巢后再服用TAM。化疗组175例,主要采用CMFVP或CMF方案。结果 绝经后患者的内分泌治疗组和化疗组5年无病生存率分别为78．4％和45．4％（P＜0．01）,5年总生存率分别为83．3％和52．9％（P＜0．05）;绝经前患者的内分泌治疗组和化疗组5年无病生存率分别为72．8％和35．7％（P＜0．01）。5年总生存率分别为80．7％和60．0％（P＜0．05）。但是Ⅰ期患者及腋淋巴结转移≥8个的患者,两者疗效差异无显著性（P＞0．05）。结论 ER阳性乳腺癌术后辅助内分泌治疗效果优于或等于化疗。     

Prognostic factors for survival after first recurrence in breast cancer: a retrospective analysis of 252 recurrent cases at a single institution

Introduction

Previous studies have shown that primary breast cancer patients with estrogen receptor (ER)-positive status have better outcomes in terms of both overall survival and disease-free intervals (DFI). However, 25.2 % of our ER-positive patients experienced recurrence. This study aimed to define factors potentially predicting survival after first recurrence in surgically treated patients with stage I–III breast cancer.

Methods

We retrospectively analyzed 252 females with recurrent breast cancer who had undergone surgery and been followed at Kyoto University Hospital in Japan. Age, clinical stage, pathological stage, axillary lymph node involvement, ER status at the time of diagnosis, progesterone receptor status, human epidermal growth factor receptor 2 status, operative method, adjuvant chemotherapy, adjuvant endocrine therapy, use of trastuzumab after recurrence, site of recurrence, DFI, and time of recurrence were examined for possible influences on survival after the first recurrence.

Results

Positive ER status and positive PR status at the time of diagnosis were significantly favorable factors of survival after first recurrence for patients with recurrence, p < 0.001 and p = 0.021, respectively. More than two sites of recurrence (p < 0.001) were associated with shorter survival time after the first recurrence on multivariate analysis. Survival of patients with recurrent breast cancer steadily improved from 1980–1994 to 1995–2008, significantly in ER-negative subgroups.

Conclusions

Positive ER status at the time of diagnosis is a powerful predictor for favorable survival after first recurrence. Survival time after first recurrence of breast cancer has steadily increased in recent decades. Advances in treatments and attitudes about breast cancer have contributed to this improvement in survival after first recurrence.     

Extent of disease and results of adjuvant radiotherapy after radical hysterectomy and pelvic lymphadenectomy in the treatment of stage IB, IIA, and IIB cervical carcinoma

Background. To identify variable prognostic factors and analyze failure patterns in uterine cervix cancer after radical operation and adjuvant radiotherapy, a retrospective analysis was undertaken. Methods. We analyzed 124 patients with uterine cervix cancer, FIGO stage IB, IIA, and IIB, treated with radical hysterectomy and pelvic lymph node dissection followed by adjuvant radiotherapy between May 1985 and May 1995. Minimum follow-up period was 24 months. All these patients were treated with full-dose external radiotherapy using a linear accelerator or high-dose-rate intracavitary radiation. Results. Overall 5-year survival rate and relapse-free survival rate were 75.4% and 73.5%, respectively. Significant prognostic factors for relapse-free survival were wall involvement thickness, lymph node location and number, parametrium involvement, tumor size, stage, uterine body involvement, and vaginal resection margin involvement. By multivariate analysis, lymph node metastasis, tumor size, and vaginal resection margin involvement were significant prognostic factors. Treatment-related failure occurred in 33 cases. In stage IIB, 5-year relapse-free survival rate was only 56%, and 9 of 22 patients had recurrence. Conclusion. Postoperative radiotherapy results are good for patients with relatively low risk factors, but the results are poor for patients with multiple high-risk factors or stage IIB. To control recurrence for patients with high-risk factors, postoperative adjuvant radiotherapy alone is not a sufficient treatment method. Considering cost-effectiveness, it may be reasonable to treat with primary radical radiotherapy for patients with stage IIB cervical cancer and poor prognostic factors instead of a radical operation and adjuvant radiotherapy or chemotherapy regimen. Further investigation should be done. Received: November 13, 1998 / Accepted: May 27, 1999     

Estrogen receptor status is the most important prognostic factor in breast cancer with ten or more positive lymph nodes

Background. In breast cancer, the prognosis worsens with increasing lymph node involvement, and aggressive therapies may prolong survival in patients with advanced breast cancer. However, there are sub-populations of patients with advanced breast cancer with ten or more diseased nodes who have long survival. Implementing appropriate treatment depends on having a realistic and well-founded view of the prognosis. Methods. Sixty-nine patients (mean follow-up, 46 months) were enrolled. All patients underwent adjuvant therapy following radical mastectomy. Thirty-seven patients relapsed after curative surgery and 40 died of their cancer. Clinicopathologic factors, tumor estrogen receptor (ER) status, progesterone receptor status, and p53 protein expression were analyzed for prognostic significance. Results. Lower lymph node stage and positive ER status reflected longer relapse-free survival (P = 0.001 and P = 0.0001, respectively). Lower tumor stage (P = 0.039), lower lymph node stage (P = 0.006), absence of distant metastasis (P = 0.006), positive ER status (P = 0.0002), and negative p53 status (P = 0.02) reflected longer overall survival. ER status was the only independent significant prognostic factor for both relapse-free and overall survival. Conclusion. ER status, an indicator of response to endocrine therapy, was the most significant factor predicting prognosis in patients with breast cancer with ten or more positive lymph nodes. Received: February 25, 1998 / Accepted: December 24, 1998     

Delayed adjuvant tamoxifen: Ten-year results of a collaborative randomized controlled trial in early breast cancer (TAM-02 trial)

Aim:Immediate adjuvant tamoxifen reduces disease recurrence andimproves survival in patients with early breast cancer. However, is it toolate to administer tamoxifen to patients who have already undergone treatment,but were unable to benefit from this adjuvant therapy? The French NationalCancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifenadministration in a randomized controlled trial. Patients and methods:From September 1986 to October 1989, womenwith primary breast cancer, who had undergone surgery, radiotherapy, and/orreceived adjuvant chemotherapy but not hormone therapy more than two yearsearlier, were randomized to receive either 30 mg/day tamoxifen or notreatment. The 10-year disease-free and overall survival rates of the twogroups of patients and of various subgroups were determined according to theKaplan–Meyer method and compared by the log-rank test. Results:This intention-to-treat analysis comprised 250 women inthe tamoxifen group and 244 in the control group. Patient characteristics(age, T stage, number of positive nodes, receptor status, and interval sincetumor treatment) were comparable in both groups. Delayed adjuvant tamoxifensignificantly improved overall survival only in node-positive patients and inpatients with estrogen receptor-positive (ER+) or progesteronereceptor-positive (PR+) tumors. Disease-free survival, however, wassignificantly improved in the global population and in several patientsubgroups (node-positive, ER+, PR+). Patients in whom the interval betweenprimary treatment and delayed adjuvant tamoxifen was greater than five yearsalso had significantly improved disease-free survival. Conclusions:Overall and disease-free survival results indicatethat delayed adjuvant tamoxifen administration (30 mg/day) is justified inwomen with early breast cancer, even if this treatment is initiated two ormore years after primary treatment.