Adjuvant treatment for early breast cancer: the Ludwig breast cancer studies

The Ludwig Breast Cancer Study Group conducted four concomitant trials involving adjuvant chemotherapy and endocrine therapy. In Ludwig I, adjuvant combination chemotherapy was used with or without prednisone to treat premenopausal and perimenopausal women with metastases in 1-3 axillary lymph nodes. The impact of adding low-dose, continuous prednisone (7.5 mg/day) to an adjuvant, chemotherapy regimen of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was investigated in a randomized trial of 491 premenopausal and perimenopausal patients with operable breast cancer and metastases in 1-3 axillary lymph nodes. As a consequence of lower hematologic toxicity, a significantly higher dose of CMF could be administered with added prednisone (P less than 0.0001). However, at the 4-year median follow-up, no significant improvement was observed in disease-free survival (DFS) (73% vs. 77%; P = 0.35) or overall survival (OS) (both 86%; P = 0.73). Induced amenorrhea was associated with a longer DFS for younger patients, those who received lower CMF doses, and those with tumors that were estrogen receptor (ER) positive. In Ludwig III, adjuvant therapy was administered to younger postmenopausal women in a study of chemotherapy plus endocrine therapy versus endocrine therapy alone versus mastectomy alone. In this randomized trial of 463 postmenopausal women 65 years of age or younger with axillary node metastases, treatment with the combination of CMF plus low-dose prednisone and tamoxifen (CMFp + T), was compared to endocrine therapy alone (p + T) or to no further treatment after total mastectomy and axillary clearance. At a median follow-up of 4 years, the DFS was 61% for the CMFp + T group, compared with 48% for the p + T group (P = 0.01) and 31% for the observation group (P less than 0.0001). The 4-year OS rates were not statistically different (76%, 67%, and 68%, respectively; P = 0.30). Treatment with CMFp + T reduced local, regional, and distant metastases and was equally effective in improving DFS in patients with ER-positive or ER-negative tumors. In Ludwig II, chemotherapy was given with or without oophorectomy in premenopausal and perimenopausal patients with metastases in 4 or more axillary nodes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Adjuvant endocrine therapy compared with no systemic therapy for elderly women with early breast cancer: 21-year results of International Breast Cancer Study Group Trial IV.

PURPOSE: Increasing numbers of older women are affected by early breast cancer, because of prolonged life expectancy and the increasing incidence of breast cancer with age. The role of adjuvant therapy for this population is still a matter of debate. We reviewed the long-term outcome of a mature trial comparing endocrine treatment versus no adjuvant therapy in older women with node-positive breast cancer. PATIENTS AND METHODS: From 1978 to 1981, 349 women 66 to 80 years of age with pathologically involved lymph nodes after total mastectomy and axillary clearance were randomly assigned to receive 12 months of adjuvant tamoxifen plus low-dose prednisone (p+T) or no adjuvant therapy. Three hundred twenty patients were eligible. RESULTS: At 21 years' median follow-up, 1 year of p+T significantly prolonged disease-free survival (DFS; P =.003) and overall survival (P =.05; 15-year DFS, 10% +/- 3% v 19% +/- 3%; hazard ratio, 0.71; 95% CI, 0.58 to 0.86). When comparing competing causes of failure (breast cancer recurrence and deaths before breast cancer recurrence), p+T was far superior in controlling breast cancer recurrence (P =.0003), but the improvement was seen mainly in soft tissue sites. Conversely, patients in the p+T group were more likely to die before a breast cancer recurrence (P =.03). CONCLUSION: This trial demonstrates that significant treatment benefits continue to be observed in older patients treated for 1 year with p+T. Despite issues relating to competing causes of failure, older breast cancer patients can benefit from treatment and should be considered for trials of adjuvant systemic therapy.     

Adjuvant chemotherapy with doxorubicin and cyclophosphamide in women with rapidly proliferating node-negative breast cancer

This prospective clinical trial was designed to assess the impact of adjuvant chemotherapy in women with rapidly proliferating node-negative breast cancer. This group has been predicted to have a 5-year disease-free survival (DFS) of 70% without adjuvant chemotherapy. In this study, 449 women with rapidly proliferating breast cancer (91% measured by S-phase fraction and 9% by histochemistry) received adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) plus tamoxifen for estrogen receptor-positive or progesterone receptor-positive cancer. The 5-year DFS was 90% (+/- 2%) and the 5-year overall survival was 94% (+/- 1%). At a median follow-up of 62 months, the strategy of administering 6 cycles of AC to women with T2 N0 cancer and 3 cycles in those with smaller T1 N0 cancers appeared to eliminate tumor size as a potential prognostic factor. Adjuvant chemotherapy with AC appears effective in reducing recurrence rates for women with rapidly proliferating node-negative breast cancer.     

118例小肿块多腋窝淋巴结转移乳腺癌患者的临床特征和预后分析

目的分析小肿块多腋窝淋巴结转移(肿块直径≤2 cm、腋窝淋巴结转移≥4个)乳腺癌患者的临床特征和预后。方法1993年1月至2003年12月我院共收治小肿块多腋窝淋巴结转移乳腺癌患者118例,对其临床病理特征、辅助治疗进行分析,以发现相关的预后因素。结果全组患者的5年总生存率为75.0%。腋窝淋巴结转移4～9个及≥10个者的5年生存率分别为89.5%和59.8%(P=0.009),术后化疗患者与未化疗患者的5年生存率分别为82.1%和53.3%(P=0.001),术后内分泌治疗者与未行内分泌治疗者的5年生存率分别为89.2%和61.9%(P=0.001)。单因素Kaplan-Merier生存分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的重要因素。Cox多因素预后分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的独立因素。结论小肿块多腋窝淋巴结转移的乳腺癌患者具有易于转移的趋势,患者预后较差,尤其是腋窝淋巴结转移≥10个的患者;肿瘤分期、辅助化疗和内分泌治疗是影响患者预后的独立因素;合理的综合治疗有可能改善小肿块多腋窝淋巴结转移乳腺癌患者的预后。     

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。     

Breast cancer patients with 10 or more involved axillary lymph nodes treated by multimodality therapy: influence of clinical presentation on outcome

PURPOSE: To analyze tumor control and survival for breast cancer patients with 10 or more positive lymph nodes without systemic disease, treated by adjuvant radiation alone or combined-modality therapy. METHODS AND MATERIALS: We reviewed the records of 309 consecutive patients with these characteristics who received locoregional radiotherapy (RT) at our institution. The majority of patients had clinical Stage II or IIIA-B disease (43% and 48%, respectively). The median number of positive axillary lymph nodes was 15 (range, 10-78). Adjuvant therapy consisted of RT alone, with or without chemotherapy, tamoxifen, and/or ovarian castration. RESULTS: The overall 5-year and 10-year disease-free survival (DFS) rates were 20% and 7%, respectively. Median DFS was higher for patients with Stage I-II compared with those with Stage IIIABC (28 vs. 19 months; p = 0.006). Median DFS for patients aged 相似文献   

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.     

Adjuvant hormone treatment and chemotherapy in postmenopausal women with operable breast cancer: a retrospective analysis.

Two hundred consecutive postmenopausal women with operable breast cancer and metastatic axillary nodes were treated during the period January - December 1981 with adjuvant chemotherapy (CMF) or hormonal treatment (tamoxifen). The distribution of receptor status (estrogen or progesterone), number of axillary metastatic nodes (less than = 3 or greater than 3), surgical treatment and size of the primary tumor were homogeneous in both groups. Receptor status and number of axillary lymph nodes were correlated with adjuvant treatment efficacy. Ten-year disease-free survival (DFS) was higher in the TAM-treated (72%) than in the CMF-treated group (52%) (p less than 0.01). In patients with less than = 3 axillary metastatic nodes, those treated with TAM had a higher DFS rate than those treated with CMF (75% vs 59%, p less than 0.01). There was no difference in DFS between CMF-and TAM-treated groups within the greater than 3 metastatic lymph node patients. In ER + primary tumors, DFS was higher in the subset treated with TAM (62%) than with CMF (51%) (p less than 0.05), whereas no difference in DFS was observed in ER- patients between the two treatment groups. Considering the TAM group, DFS was better (p less than 0.01) for ER+ cases than for ER- cases only at 5 years of observation. In the CMF group, DFS was not influenced by ER status. PgR content did not affect DFS in either adjuvant treatment group.     

1-hexylcarbamoyl-5-fluorouracil + cyclophosphamide + tamoxifen versus CMF + tamoxifen in women with lymph node-positive breast cancer after primary surgery: a randomized controlled trial

We studied the usefulness of the oral 5-FU anti-cancer drug 1-hexylcarbamoyl-5-fluorouracil (HCFU) + cyclophosphamide (CPM) + tamoxifen (TAM) (HCT group) in comparison with CMF + TAM (CMFT group) in adjuvant therapy for breast cancer by a non-inferiority study based on a multi-institutional joint study. Clinical stage I, II primary breast cancers with histologically positive axillary lymph node metastasis were randomly assigned to the HCT group or the CMFT group after primary surgery. We registered 136 cases (HCT group 68 cases, CMFT group 68 cases). No significant difference in the 5-year overall survival rate (OS) and the 5-year disease-free survival rate (DFS) was found between the two groups. In the stratified analysis, DFS in cases in which the number of metastatic lymph nodes was 1-3 was significantly better in the HCT group (HCT group 84.3%, CMFT group 69.4%, log-rank test p=0.0496). No significant difference in the total incidence of adverse effects was found between the two groups, but there were significantly less adverse effects of grade 2 or over in the HCT group (p=0.034). The QOL survey at 3 months after surgery showed a significant decline of the QOL regarding lassitude, degree of difficulty in daily life, satisfaction with treatment and present mood in the CMFT group. Study results suggest that 2-year HCT therapy including the oral 5-FU anti-cancer drug HCFU is a useful adjuvant therapy which can replace CMFT therapy in early breast cancer cases with 3 or lower metastatic lymph nodes.     

Locoregional failure of postmastectomy patients with 1-3 positive axillary lymph nodes without adjuvant radiotherapy

PURPOSE: To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT). MATERIALS AND METHODS: Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1-3 positive axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months. RESULTS: Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04), tumor size >==3 cm (p = 0.002), negative estrogen receptor protein status (p = 0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size (p = 0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor >==3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of 66.7% (95% CI 42.8-90.5%) compared with 7.8% (95% CI 2.2-13.3%) for the low-risk group (with 0-2 factors; p = 0.0001). For the 110 patients who received no adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9 of 17, 95% CI 24.6-73.4%). For patients without LRR, it was 13.3% (15 of 93, 95% CI 6.3-20.3%; p = 0.0001). The 4-year survival rate for patients with and without LRR was 75.1% (95% CI 53.8-96.4%) and 88.7% (95% CI 82.1-95.4%; p = 0.049), respectively. LRR was independently associated with a higher risk of distant metastasis and worse survival in multivariate analysis. CONCLUSION: LRR after mastectomy is not only a substantial clinical problem, but has a significant impact on the outcome of patients with T1 or T2 primary tumor and 1-3 positive axillary nodes. Patients with risk factors for LRR may need adjuvant RT. Randomized trials are warranted to determine the potential benefit of postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1-3 positive nodes.     

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised,controlled trial

BackgroundDespite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy.Patients and methodsThis randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety.ResultsBetween 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1–4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole.ConclusionThese results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy.Clinical Trials NumberAustralian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493     

Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients

Ten-year follow-up results are presented of an adjuvant clodronate trial in patients with primary breast cancer. Between 1990 and 1993, 299 women with primary node positive breast cancer were randomized to oral clodronate 1600 mg daily (149) or controls (150) for 3 years. All patients received adjuvant chemo- or endocrine therapy. Within 10 years bone metastases were detected at the same frequency in the clodronate and control groups: 44 (32%) vs. 42 (29%), respectively, (p=0.35). The frequency of non-skeletal recurrences (visceral and local) was significantly higher in the clodronate group 69 (50%) as compared with the controls 51 (36%) (p=0.005). Ten-year disease-free survival (DFS) remained significantly lower in the clodronate group (45% vs. 58%, p=0.01, respectively). This was especially seen in oestrogen receptor negative patients (25% vs. 58%, p=0.004, respectively). No significant overall survival difference was found between the groups. As previously reported 3-year adjuvant clodronate treatment did not prevent the development of bone metastases in node-positive breast cancer patients. A negative effect of clodronate on DFS by increasing the development of visceral metastases was still seen at 10 years, but this did not significantly compromise overall survival.     

Profile of prognostic factors in 1022 Indian women with early-stage breast cancer treated with breast-conserving therapy

PURPOSE: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. METHODS AND MATERIALS: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). RESULTS: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women. The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age < or =40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). CONCLUSION: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.     

青年女性乳腺癌155例临床分析

目的研究青年女性乳腺癌患者的临床特点、生存期及预后影响因素。方法回顾性分析155例35岁以下女性乳腺癌患者的临床资料,并进行随访和统计分析。结果155例患者中激素受体阳性占61．6％（77／125）,激素受体阳性和阴性患者的中位生存时间分别是119．0和51．3个月（P〈0．01）,其5年生存率分别为68％和33％。辅助他莫昔芬（TAM）治疗占47．1％（73／155）,中位生存时间182个月,较未辅助TAM者显著延长生存期（P〈0．05）。全组患者的中位无瘤生存期24个月,中位生存时间91个月,3、5、10年生存率分别为79％、60％和5．1％。COX多因素分析显示影响预后的主要因素有肿瘤大小、腋淋巴结转移、辅助内分泌治疗和Her-2过表达。激素受体阳性可能是预后的参考因素。结论≤35岁女性乳腺癌患者的预后影响因素是肿瘤大小、腋淋巴结转移、辅助内分泌治疗和Her-2表达情况。青年乳腺癌患者只要经过系统的综合治疗预后不差,仍可获得长期生存。     

A single perioperative adjuvant chemotherapy course for node-negative breast cancer: five-year results of trial V. International Breast Cancer Study Group (formerly Ludwig Group).

Twelve hundred seventy-five patients who were defined as having node-negative breast cancer were evaluated in a randomized trial that compared a single cycle of combination chemotherapy started within 36 hours of surgery (848 patients) with no adjuvant treatment (427 patients). The chemotherapy consisted of intravenous cyclophosphamide, methotrexate, and fluorouracil given on days 1 and 8. Leucovorin (given on days 2 and 9) was added to the regimen to decrease severe toxic effects attributed to drug interaction between nitrous oxide used in anesthesia and methotrexate given in the immediate postoperative period. At a median follow-up of 60 months, the 5 year disease-free survival (DFS) percentages (+/- SE) were 74% +/- 2% for the treated group, and 68% +/- 2% for the no adjuvant therapy group. The estimated hazard ratio [95% confidence interval (CI)] was 0.78 (0.63 to 0.96); P = .02, representing a 22% +/- 9% relative reduction in the risk of relapse. The overall survival (OS) difference was not statistically significant with 5-year OS percentages of 88% +/- 1% for the treated group, and 85% +/- 2% for the control group [estimated hazard ratio (95% CI) = 0.85 (0.62 to 1.16); P = .31]. A subgroup analysis by menopausal status and by estrogen-receptor (ER) status revealed that the treatment effect was largest among the postmenopausal women with ER-negative tumors. The 5-year DFS percentages were 79% +/- 4% and 56% +/- 7%, and the OS percentages were 91% +/- 3% and 70% +/- 6%, for the treated and control groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

T1-2N1M0期乳腺癌新辅助化疗后疗效分析及放疗选择的探讨

目的 评价T_1-2N₁M₀期乳腺癌新辅助化疗后辅助放疗对LC率的影响及地位。方法收集2005—2010年间收治的新辅助化疗患者资料,筛选出T_1-2N₁M₀人群,并对其辅助放疗的临床结果进行分析。共入组T_1-2N₁M₀患者144例,中位年龄45岁(23~72岁)。结果 术后30例(21%)获得乳腺原发灶和腋窝淋巴结pCR者均接受了辅助放疗,45例仅腋窝淋巴结阳性转阴性者中10例未接受辅助放疗,69例腋窝淋巴结转移仍为阳性者中6例未接受放疗,其余患者均接受了辅助放疗。全组中位随访时间88个月,46例复发转移(32%),其中pCR者5年LR率为3.0%。5年LR率新辅助化疗后腋窝淋巴结阳性转阴性者放疗组为7%、未放疗组为16%(P=0.181),腋窝淋巴结仍为阳性者放疗组为15.9%、未放疗组为33%(P=0.267)。全组pCR者DFS时间较非pCR者延长(P=0.017)。结论 新辅助化疗后获pCR者DFS期优于未获pCR者,获pCR患接受辅助放疗的LR率较低,腋窝淋巴结阳性转阴性者未能从术后辅助放疗中获益,而腋窝淋巴结转移仍为阳性者的LR率高,辅助放疗有获益趋势。     

Ⅰ—Ⅱ期乳腺癌保乳术后放疗的临床疗效及预后分析

目的 分析Ⅰ—Ⅱ期乳腺癌保乳术后放疗的临床疗效和预后因素。方法 回顾分析1999—2013年1376例Ⅰ、Ⅱ期(T1-2N0-1/T3N0)单侧乳腺癌保乳术后放疗的疗效。930例(67.6%)同时接受化疗,先放疗后化疗 517例,先化疗后放疗 413例。1055例(76.7%)患者接受内分泌治疗,86例(39.6%) HER-2阳性患者接受靶向治疗。用Kaplan-Meier计算生存率并Logrank法单因素分析,Cox法多因素分析。结果 中位随访55个月,10年样本量 90例。全组5、10年OS率分别为98.6%和91.5%,DFS率分别为94.6%和82.8%。多因素分析显示年龄(P=0.016)、T分期(P=0.006)、N分期(P=0.004)、脉管癌栓(P=0.038)和放疗距手术时间(P=0.048)是DFS独立预后因素。保乳术后单纯放疗组多因素分析显示,N分期(P=0.044)和ER水平(P=0.026)是DFS独立预后因素。结论 Ⅰ—Ⅱ期乳腺癌保乳术后以放疗为主的综合治疗模式临床疗效满意。影响DFS率的因素包括年龄、T分期、N分期、脉管癌栓和放疗距手术时间。保乳术后单纯放疗组的DFS率和N分期与ER水平有关。     

Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93.

BACKGROUND: Toremifene is a chlorinated derivative of tamoxifen, developed to improve its risk-benefit profile. The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials for peri- and postmenopausal patients with node-positive breast cancer to compare toremifene versus tamoxifen as the endocrine agent and simultaneously investigate a chemotherapy-oriented question. This is the first report of the endocrine comparison after a median follow-up of 5.5 years. PATIENTS AND METHODS: 1035 patients were available for analysis: 75% had estrogen receptor (ER)-positive primary tumors, the median number of involved axillary lymph nodes was three and 81% received prior adjuvant chemotherapy. RESULTS: Toremifene and tamoxifen yielded similar disease-free (DFS) and overall survival (OS): 5-year DFS rates of 72% and 69%, respectively [risk ratio (RR)=0.95; 95% confidence interval (CI)=0.76-1.18]; 5-year OS rates of 85% and 81%, respectively (RR = 1.03; 95% CI = 0.78-1.36). Similar outcomes were observed in the ER-positive cohort. Toxicities were similar in the two treatment groups with very few women (<1%) experiencing severe thromboembolic or cerebrovascular complications. Quality of life results were also similar. Nine patients developed early stage endometrial cancer (toremifene, six; tamoxifen, three). CONCLUSIONS: Toremifene is a valid and safe alternative to tamoxifen in postmenopausal women with endocrine-responsive breast cancer.     

Prognostic and Predictive Factors of Early Breast Cancer

OBJECTIVE To identify risk factors for relapse and death in patients with T1 to T2 breast cancer with 0-3 positive axillary lymph nodes.METHODS The case files of 540 breast cancer patients with T1-T2 tumors with 0-3 positive nodes were reviewed retrospectively. Ten-year locoregional recurrence (LRR), distant recurrence (DR), disease-free survival (DFS) and overall survival (OS) of the patients were analyzed. Univariate statistical analysis and Cox proportional hazards models were carried out with SPSS so ware v.16.0.RESULTS The median follow-up of all the patients was 7.2 years. On multivariate analysis, > 20% positive axillary nodes was the only variable that influenced LRR adversely (hazard ratio[HR], 12.816; 95% confidence interval, 4.657-35.266, P < 0.001); > 20% positive axillary nodes and ductal carcinoma were variables that influenced DR adversely (HR, 11.088, 95% confidence interval, 3.807-32.297, P < 0.001; HR, 0.390, 95% confidence interval, 0.179-0.851, P = 0.018); 1-3 positive axillary nodes and > 20% positive axillary nodes were the only variables that had negative e. ect on 10-year OS (HR, 2.110, 95% confi dence interval, 1.364-3.264, P = 0.001; HR, 10.244, 95% confidence interval, 3.497-30.011, P < 0.001) and they were also adverse prognostic variables on 10-year DFS (HR, 1.634, 95% confidence interval, 1.171-2.279, P = 0.004; HR, 7.339, 95% confi dence interval,2.906-18.530, P < 0.001).CONCLUSION Axillary lymph nodal status is the only risk factor with a signifi cant impact on 10-year LRR, DR, OS and DFS.Patients with T1-T2 breast cancer with 0-3 positive lymph nodes have the LRR and DR of over 10 years, and the OS and DFS of less than 10 years, compared to patients with negative lymph nodes.Histology in primary tumors is a signifi cant prognostic factor for the 10-year DR.