When May Adjuvant Radiotherapy be Avoided in Operable Breast Cancer?

Randomised trials in which the omission of radiotherapy has been tested after breast-conserving surgery, with or without adjuvant systemic therapy, show a significant four- to five-fold reduction in local recurrence. As yet, no subgroup of women managed by breast-conserving surgery has been identified from whom radiotherapy can be withheld. Few randomised data have been published on the effect of omission of radiotherapy on local control, quality of life and costs, particularly in older women for whom the risk of local recurrence is generally lower. Ongoing trials are evaluating the role of radiotherapy in this population of low risk, older women. Adjuvant radiotherapy after breast-conserving surgery or mastectomy significantly reduces the incidence of local recurrence. In women who have had a mastectomy at high risk of recurrence (> 20% risk of recurrence at 10 years), adjuvant radiotherapy improves survival if combined with adjuvant systemic therapy. Among women with T3 tumours, and those with four or more involved axillary nodes treated by mastectomy, postoperative radiotherapy is the standard of care. For women at intermediate risk of recurrence (i.e. <15% 10-year risk of recurrence after surgery and systemic therapy alone), with one to three involved nodes or node negative with other risk factors, the role of radiotherapy is unclear. Clinical trials to assess the role of postmastectomy radiotherapy (PMRT) in this setting are needed. For pT1-2, pNO tumours without other risk factors, there is no evidence at present that PMRT is needed.     

A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37

In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >or= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2- positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator.     

A comparative analysis of radiotherapy use and patient outcome in males and females with breast cancer.

BACKGROUND: The aim was to determine whether gender was a significant prognostic factor for post-mastectomy relapse, after accounting for known prognostic factors and delivery of radiotherapy. PATIENTS AND METHODS: All patients diagnosed with invasive breast cancer between 1 January 1989 and 31 December 1998 who had undergone total mastectomy as primary therapy were identified from the British Columbia Cancer Agency's Breast Cancer Outcomes Unit database. Patients with pT4 or M1 disease were excluded. A comparison of patient, tumour and treatment factors was made between males and females. Outcomes were analysed in terms of locoregional-relapse free survival, breast cancer-specific survival and overall survival. RESULTS: Sixty males and 4181 females were identified. Multivariable analysis revealed increased tumour size, positive margin status, delivery of chemotherapy, positive nodal status and male gender to be significantly associated with the use of post-mastectomy radiotherapy. Multivariable analysis revealed tumour size, nodal status, tumour grade and presence of vascular space invasion to be significantly associated with locoregional recurrence. Gender was not a prognostic factor for locoregional recurrence, breast cancer-specific survival or overall survival on univariable or multivariable analysis. CONCLUSIONS: These data suggest that gender is not a prognostic factor in patients undergoing mastectomy for early stage breast cancer. Men having mastectomy for breast cancer should receive adjuvant radiotherapy following guidelines similar to those developed for females.     

Adjuvant therapy of resected non-small-cell lung cancer

Surgical resection of early-stage non-small-cell lung cancer (NSCLC) remains the standard of care in patients fit for surgery. Careful preoperative staging is imperative, as is pathologic documentation of the mediastinal nodal contents. Adjuvant postoperative thoracic radiation therapy (RT) clearly has an impact in reducing locoregional recurrence but has no clear impact on survival. The Postoperative RT (PORT) metaanalysis raised concerns about PORT, particularly in stage I/II NSCLC, suggesting it may negatively impact survival. This was not a concern in stage III NSCLC, in which the risk of locoregional recurrence is higher. However, distant recurrence remains the dominant pattern in resected NSCLC, suggesting that the majority of patients with early-stage resected NSCLC harbor occult micrometastatic disease. Historically, the role of adjuvant chemotherapy has been controversial, and its routine use was not supported by the published data, which consisted of a small number of underpowered trials using inadequately delivered, antiquated chemotherapy. More recently, larger trials have been reported with conflicting results. Like adjuvant PORT, chemotherapy combined with RT has not improved survival over PORT alone. The use of adjuvant cisplatin-based therapy did not show a survival advantage in the Adjuvant Lung Project Italy study but did in the International Adjuvant Lung Trial, creating controversy in the routine implementation of adjuvant therapy in all patients. Recently completed randomized trials by the Cancer and Leukemia Group B and the National Cancer Institute of Canada provide convincing evidence of a substantial benefit from adjuvant therapy in well-staged and completely resected stage I/II NSCLC. Currently, the totality of the data supports a discussion with patients with resected NSCLC regarding the potential benefits of adjuvant therapy.     

Comparison of recurrence and survival rates after breast-conserving therapy and mastectomy in young women with breast cancer

Multiple randomized trials have demonstrated that breast-conserving therapy with partial mastectomy and radiotherapy provides survival equivalent to that seen with mastectomy for patients with early-stage breast cancer. Breast-conserving therapy has been associated with better quality of life relative to mastectomy and has become the standard of care for patients with early-stage breast cancer. Young age has been identified as a risk factor for recurrence and death from breast cancer. Some studies have suggested that young women (less than 35 or 40 years of age) have inferior outcomes with breast-conserving therapy, implying that such women may be better served by mastectomy. On review of the available literature, there is no definitive evidence that mastectomy provides a consistent, unequivocal recurrence-free or overall survival benefit over breast-conserving therapy. However, available meta-analyses have not compared outcomes in young women specifically, and such analyses should be performed. In the interim, breast-conserving therapy is not contraindicated in young women (less than 40 years of age) and can be used cautiously; however, such women should be advised of the lack of unequivocal data proving that survival is equivalent to that with mastectomy in their age group.     

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck

Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3-4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100 mg/m(2) every 21 days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63 Gy for high-risk patients and at least 57 Gy for low risk patients.     

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes

BACKGROUND: Adjuvant therapy for women with T1-T2 breast carcinoma and 1-3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes. METHODS: The study cohort was comprised of 542 women with pathologic T1-T2 breast carcinoma who had 1-3 positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier (KM) LRR, distant recurrence (DR), and overall survival (OS) rates stratified by the number of positive lymph nodes, the number of dissected lymph nodes, and the percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. RESULTS: The median follow-up was 7.5 years. LRR, DR, and OS rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes, but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in LRR was observed was 25% positive lymph nodes (the 10-year KM LRR rates were 13.9% and 36.7% in women with < or = 25% and > 25% positive lymph nodes, respectively; P < 0.0001). Higher DR rates and lower OS rates were observed among patients who had > 25% positive lymph nodes compared with patients who had < or = 25% positive lymph nodes (DR: 53.0% vs. 30.3%, respectively; P < 0.0001; OS: 43.4% vs. 62.6%, respectively; P < 0.0001). In the multivariate analysis, the percentage of positive lymph nodes and the histologic grade were significant, independent factors associated with LRR, DR, and OS. CONCLUSIONS: The presence of > 25% positive lymph nodes was an adverse prognostic factor in patients with 1-3 positive nodes and may be used to identify patients at high risks of postmastectomy locoregional and distant recurrence who may benefit with adjuvant radiotherapy and more aggressive systemic therapy regimens.     

Adjuvant radiotherapy in breast cancer--the treatment of lymph node areas

Adjuvant radiotherapy decreases the risk of locoregional recurrences threefold, according to the results of many randomized trials and overviews. In patients treated with total mastectomy, the risk of local recurrence is mainly related to the number of involved axillary nodes, i.e. about 25%, 35% and 55% at 10 years when 1-3, 4-9 and 10 or more nodes are involved, respectively. In contrast, at 10 years, less than 15% of patients with negative axillary nodes relapse locally. The effect of adjuvant radiotherapy on distant metastases and overall survival is a controversial issue. On the one hand, recent results are compatible with the existence of a mechanism of secondary dissemination generated from locoregional tumor nests. The beneficial effect of radiotherapy can be observed whether with or without adjuvant systemic treatment. On the other hand, a deleterious late toxic effect, mainly cardiac, has also been shown. The importance of improvements in radiation techniques and quality assurance to obtain a positive balance in terms of overall survival is emphasized.     

Regional Nodal Radiotherapy in Early-Stage Breast Cancer: Where Are We in 2016?

The goal of locoregional treatment in early-stage breast cancer patients is to eradicate residual locoregional microscopic disease in order to maximize locoregional control, to minimize seeding of distant metastatic sites, and ultimately to improve overall survival. Recently published landmark randomized trials demonstrate that the addition of regional nodal radiotherapy to breast conserving therapy or mastectomy in node positive or high-risk node negative women not only improves locoregional control but also decreases distant metastasis with a trend towards improved overall survival with a favorable toxicity profile. Certain node-positive early-stage breast cancer patients, however, have low rates of axillary recurrence and high rates of breast cancer-specific survival even with sentinel lymph node excision alone without axillary lymph node dissection. Herein, we review the recent developments in regional nodal management and reconcile the apparent conflict between the surgical and radiotherapy literature. In this context, we provide guidance as to the patients appropriate for regional nodal radiotherapy in 2016 and highlight important treatment considerations to minimize long-term toxicity.     

早期乳腺癌患者根治术后的放射治疗

目的 探讨早期乳腺癌患者根治术后放射治疗的作用。方法 回顾分析605例T1－2N0－1M0乳腺癌患者接受乳腺癌根治性手术后的治疗情况,149例患者单纯手术,135例术后放疗,113例术后化疗或三苯氧胺治疗,208例术后化疗或三苯氧胺治疗加放疗。生存分析采用Kaplan-Meier方法和Log rank检验。结果 单纯手术组与手术＋放射治疗组的10年局部区域复发率分别为18．7％和7．5％（P＝0．017）,总生存率分别为82．1％和81．1％（P＝0．618）,无瘤生存率分别为65．2％和71．6％（P＝0．457）。术后放射治疗能显著降低局部区域复发率,但对总生存率和无瘤生存率无明显影响。单纯术后全身治疗组和术后全身治疗＋放射治疗组的10年局部区域复发率分别为21．1％和9．5％（P＝0．001）,总生存率为75．5％和85．0％（P＝0．020）,无瘤生存率为59．3％和70．2％（P＝0．003）。术后放射治疗＋化疗不仅可显著降低局部区域复发率,还可提高无瘤生存率和总生存率。对窝淋巴结数≥4个接受全身治疗的患者,放射治疗有明显的疗效,能显著降低局部区域复发率,提高无瘤生存率和总生存率,这组患者未放射治疗组和放射治疗组的10年局部区域复发率分别为40．1％和15．1％（P＝0．001）,总生存率为54．4％和67．1％（P＝0．040）,无瘤生存率为30．5％和57．3％（P＝0．001）。结论 对早期乳腺癌窝淋巴结转移≥4个的患者,术后放疗能显著降低局部区域复发率,提高生存率。建议对这部分患者做常规术后放疗。     

Low risk of locoregional recurrence of primary breast carcinoma after treatment with a modification of the Halsted radical mastectomy and selective use of radiotherapy

BACKGROUND: The purpose of the current study was to evaluate the locoregional recurrence rate after treatment of patients with operable breast carcinoma with a modification of the Halsted radical mastectomy and the selective use of radiotherapy and to identify risk factors for locoregional recurrence. METHODS: Between 1979-1987, 691 consecutive patients underwent mastectomy after a negative biopsy of the axillary apical lymph nodes. The median age of the patients was 59 years (range, 26-89 years). The clinical tumor size was < 2 cm in 72 patients, 2-5 cm in 387 patients, and >5 cm in 169 patients; 16 patients had a T4 tumor. Surgery was comprised of a modification of the Halsted radical mastectomy, including at least part of the pectoralis major muscle and the entire pectoralis minor muscle, in 573 patients; 303 patients had positive axillary lymph nodes. Adjuvant radiotherapy to the chest wall and regional lymph nodes was given to 74 patients, whereas an additional 414 patients underwent irradiation to the internal mammary and medial supraclavicular lymph nodes. The median follow-up was 91 months. RESULTS: The actuarial overall survival rate was 82% at 5 years and 63% at 10 years. The 10-year chest wall and regional lymph node control rates, including patients with prior distant failures, were 95% and 94%, respectively. The only two significant prognostic factors for locoregional recurrence on multivariate analysis were lymph node status and pathologic tumor size. CONCLUSIONS: Excellent locoregional control can be achieved with a modified technique of radical mastectomy in patients with negative apical biopsy and the selective use of comprehensive radiotherapy. These results may serve as a reference outcome for comparison with other locoregional treatment strategies.     

Survival and Pattern of Failure Following Locoregional Recurrence of Breast Cancer

This study analyzed prognostic factors at primary diagnosis and at first recurrence for impact on survival after isolated locoregional failure. The aims were: (1) assessment of prognostic factors for time to second locoregional failure, distant failure, and survival in isolated locoregional recurrence of breast cancer after mastectomy; and (2) investigation of the impact of a second locoregional failure on dissemination and survival.Between 1983 and 1985, 99 patients who had undergone mastectomy and then developed isolated local and/or regional recurrences, were treated with radical excision and radiotherapy; none of these patients had distant metastases. Survival and the times to second local failure and distant metastasis were analyzed according to potential prognostic factors.The median follow-up was 123 months; 38 patients were still alive. Median survival was 89 months and the 10-year survival rate was 38%, with no difference between local and regional recurrences. A total of 43 patients developed a second locoregional recurrence after a median of 73 months; primary tumour size and initial node status were significant independent prognostic factors. The annual hazard rates for recurrence were similar for patients developing local failure or systemic recurrence. The 10-year rate of dissemination was 49% for patients with locoregional control, compared with 51% for patients who had a second locoregional recurrence. The prognostic factors for survival were node status at mastectomy and haemoglobin level at first recurrence.The development of a second locoregional recurrence was not associated with an increased risk of dissemination or reduced survival. Differences in prognostic factors for locoregional control and distant metastases suggest that these recurrences represent different biological entities that require different treatment strategies. However, as the achievement of locoregional control had no influence on prognosis, the use of systemic adjuvant therapy may be warranted in a subset of these patients.     

Postmastectomy radiotherapy in women with breast cancer metastatic to one to three axillary lymph nodes

The influence of postmastectomy radiotherapy on survival has long been debated. Early randomized trials established a clear role for adjuvant postmastectomy chest wall radiotherapy (PMCWRT) in reducing locoregional recurrence (LRR), and PMCWRT became standard therapy for patients at high risk of LRR: those with T3 or T4 tumors and four or more involved lymph nodes. However, without effective systemic therapy, distant metastases limited any effect of improved local control on overall outcome, and radiotherapy showed no benefit in survival. In fact, early meta-analyses showed a negative impact of radiotherapy on survival. As data and techniques matured, a favorable influence of PMCWRT on breast cancer-specific mortality emerged but was offset by a radiotherapy-related increase in vascular mortality. Improvements in radiotherapy delivery to increase efficacy and reduce toxicity, restriction of PMCWRT to patients at intermediate or high risk of LRR after mastectomy, and improved distant control of disease with systemic therapy are expected to bring the greatest likelihood of a survival advantage from locoregional control. Three randomized trials with sufficient follow-up meet these criteria. All demonstrate significant improvement in overall survival with PMCWRT. However, the trials were not designed to specifically address the benefit of PMCWRT in patients at intermediate risk of LRR (those with T1 or T2 tumors and one to three involved lymph nodes). These findings have been discussed in a host of publications and conferences in light of historical negative results. This review focuses on the recent data on PMCWRT in patients with one to three involved nodes.     

靶向治疗对HER-2阳性改良根治术后未放疗乳腺癌患者复发影响——单中心大宗病例倾向评分匹配回顾分析

目的 评估乳腺癌抗HER-2靶向治疗的局部区域作用及对放疗决策的影响。方法 回顾分析2009-2014年本中心诊治的HER-2阳性、改良根治术后未放疗患者 1398例,其中接受辅助靶向者 370例。靶向治疗以单药曲妥珠单抗为主。结果 接受靶向治疗显著改善无瘤生存、总生存,也降低局部区域复发(LRR),多因素分析发现靶向治疗提高LRRFS (P=0.06)。倾向评分匹配其他预后因素后,有、无靶向治疗 5年LRR率分别为4.4%、6.6%(P=0.070)。亚组分析显示靶向治疗的局控优势在病理分级Ⅰ-Ⅱ级患者中显著(2.5%、5.9%,P=0.046);而原本需考虑放疗的亚组(pN1)靶向治疗后复发风险依旧相对高,有、无靶向治疗 5年LRR率分别为8.2%、12.3%(P=0.150)。激素受体阳性者靶向治疗的获益明显。接受靶向治疗且有良好预后因素的患者 5年LRR率可在5%以下。结论 以单药曲妥珠单抗为主的抗HER-2靶向治疗可提高改良根治术后患者LRRFS,但有放疗适应证的患者因复发率较高暂不能免于放疗,新开展的双单抗辅助靶向有望进一步改善局控,亦需进一步亚组分析寻找低危患者。     

Comparison of Conventional and Hypofractionated Radiotherapy in Breast Cancer Patients in Terms of 5-Year Survival,Locoregional Recurrence,Late Skin Complications and Cosmetic Results

Bckground: Adjuvant radiation therapy is commonly administered following breast-conserving surgery for breast cancer patients. Hypofractionated radiotherapy can significantly reduce the waiting time for radiotherapy, working load on machines, patient visits to radiotherapy departments and medical costs. Material/Methods: Fifty-two patients with operable breast cancer (pT1-3pN0M0) who underwent breast conservation surgery in Tehran Cancer Institute during January 2011 to January 2012, were randomly assigned to undergo radiotherapy in two arms (hypofractionated radiotherapy arm with 30 patients, dose 42.5 Gy in 16 fractions; and conventional radiotherapy arm with 22 patients, dose 50 Gy in 25 fractions). W compared these two groups in terms of overall survival, locoregional control, late skin complications and cosmetic results. Results: At a median follow-up of 52.4 months (range: 0–64 months), the follow-up rate was 82.6%. Overall, after 60 months, there was no detectable significant differences between groups regarding cosmetic results (p = 0.857), locoregional control or survival. Conclusions: The results confirm that hypofractionated radiotherapy with a subsequent boost is as effective as conventional radiotherapy, is well-tolerated and can be used as an alternative treatment method following breast conservation surgery.     

Valeur pronostique des sous-types moléculaires et du Ki67 pour les cancers du sein indemnes d’envahissement ganglionnaire après mastectomie : expérience de l’institut Curie–hôpital René-Huguenin et revue de la littérature

PurposeTo evaluate the prognostic value of Ki67 expression, breast cancer molecular subtypes and the impact of postmastectomy radiotherapy in breast cancer patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy.Patients and methodsSix hundred and ninety-nine breast cancer patients with pN0 status after modified radical mastectomy, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumours were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of locoregional recurrence associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors.ResultsAt a median follow-up of 56 months, 17 patients developed locoregional recurrence. Five-year locoregional recurrence-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the postmastectomy radiotherapy (n = 191) and no-postmastectomy radiotherapy (n = 508) subgroups. No constructed subtype was associated with an increased risk of locoregional recurrence. A Ki67 above 20% was the only independent prognostic factor associated with increased locoregional recurrence (hazard ratio, 4.18; 95% CI, 1.11 to 15.77; P < 0.0215). However, postmastectomy radiotherapy was not associated with better locoregional control in patients with proliferative tumours.ConclusionKi67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after modified radical mastectomy. The benefit of adjuvant radiotherapy in patients with proliferative tumours should be further investigated in prospective studies.     

Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control of node-positive breast cancer: cancer and leukemia group B 9344.

PURPOSE: We compared radiotherapy (RT) delivery and locoregional control in patients with node-positive breast cancer randomly assigned on Cancer and Leukemia Group B 9344 to receive adjuvant doxorubicin/cyclophosphamide (AC) with patients assigned to receive AC followed by paclitaxel (AC+T). METHODS: Eligible patients were randomly assigned to receive adjuvant AC versus AC+T chemotherapy. RT was required if breast-conserving surgery was performed but was elective after mastectomy. Information about RT delivery was retrospectively collected. Cumulative incidence of locoregional recurrence (LRR), use of elective RT, and RT delivery were compared between treatment arms. RESULTS: For patients treated with breast-conserving surgery and RT, the 5-year cumulative incidence of isolated LRR was 9.7% in the AC arm and 3.7% in the AC+T arm (P = .04) and of LRR as any component of failure was 12.9% versus 6.1%, respectively (P = .04). Although LRR rates in patients who did not receive postmastectomy RT were lower in the AC+T arm, the difference was not statistically significant. Despite the lack of protocol guidelines, RT use did not differ between arms, nor did RT dose, treatment interruption, or completion. CONCLUSION: Despite the delay to RT during additional chemotherapy, adjuvant AC+T afforded better local control than AC alone in patients treated with breast-conserving therapy. Addition of paclitaxel did not adversely affect delivery or ability to tolerate RT, as indicated by similar rates of completion of timely, full-dose RT between arms.     

The sequencing of radiation therapy and chemotherapy after mastectomy in premenopausal women with breast cancer

OBJECTIVE: The purpose of this study was to evaluate the prognostic importance of the sequencing of radiation therapy and chemotherapy after mastectomy in high-risk premenopausal women with breast cancer in addition to other known prognostic factors in the literature. METHODS: In this retrospective study, 176 premenopausal women with breast cancer were evaluated. The median age at referral was 39 years (range, 28-59 years); 106 patients had stage II and 70 had stage III disease. All were subjected to mastectomy. The median number of lymph nodes removed was 19. The influence of age, histological grade, number of nodes removed, number of positive nodes, tumor size, estrogen receptor status, lymphovascular invasion and sequencing of radiotherapy and chemotherapy on 5-year locoregional disease-free survival, 5-year systemic disease-free survival, 5-year disease-free survival and 5-year cancer-specific survival were studied. RESULTS: The 5-year locoregional disease-free survival was 94% for the entire patient population. Because of the small number of locoregional recurrences, none of the evaluated factors was prognostically significant for locoregional recurrence. The 5-year systemic disease-free, disease-free and cancer-specific survival rates were 72, 70 and 77%, respectively. On multivariate analysis of host, tumor and treatment-related factors, the number of positive nodes [RR 1.9 (95% CI: 1.36-2.63), RR 2 (1.46-2.84 ) and RR 1.8 (1.3-2.71), respectively], histopathological grade [RR 1.8 (95% CI: 1.24-2.65), RR 1.9 (1.34-2.88), RR 2.5 (1.65-4.07), respectively], estrogen receptor status [RR 3.5 (95% CI: 1.5-8.6), RR 3.9 (1.64-9.41), RR 2.5 (1.05-6.24), respectively] and the sequencing of radiotherapy and chemotherapy [RR 1.6 (95% CI: 1.17-2.39), RR 1.7 (1.25-2.54), RR 1.6 (1.14-2.43), respectively] were all significant independent predictors of outcome. CONCLUSIONS: Our results show that in addition to traditional prognostic factors, the sequencing of radiation therapy and chemotherapy also predict for increased risk of any type of recurrence or further tumor death.     

Breast-conserving therapy for stage I-II breast cancer in elderly women

PURPOSE: To assess breast-conserving therapy results in elderly patients with early-stage breast cancer (clinical Stage I-II). METHODS AND MATERIALS: Between 1979 and 1998, 196 women (200 treated breasts) aged > or =70 years (median age, 72.5 years) were treated with breast-conserving therapy (lumpectomy or quadrantectomy with axillary lymph node dissection and radiotherapy). Pathologic axillary node involvement was found in 51 patients (28%). Two-thirds of patients received tamoxifen, and 16% received chemotherapy. RESULTS: At a median follow-up of 59 months, 3 patients (1.5%) had developed local recurrence and 20 (10.2%) distant metastases. The overall survival rate was 81% and 62% at 5 and 10 years, respectively. The corresponding disease-specific survival rates were 92% and 88%. Axillary nodal involvement was the only statistically significant risk factor for the development of metastases (p = 0.0035). Arm mobility impairment and arm lymphedema each occurred in 5 patients. In another 5 patients, a thromboembolic event occurred during tamoxifen treatment. CONCLUSION: Elderly women tolerate breast-conserving therapy, including radiotherapy, well and have excellent rates of locoregional control and disease-specific survival.     

The role of radiotherapy in patients undergoing mastectomy for carcinoma of the breast

Several factors, including T stage, nodal involvement, grade, the presence of lymphovascular invasion, and possibly involved or close surgical margins, have been found to affect local recurrence after mastectomy. The majority of recurrences will occur in the first 5 years and 50% of patients will have metastatic disease at the time of recurrence. Early studies on the use of adjuvant radiotherapy are difficult to interpret owing to poor radiotherapy techniques, inadequate dose or a variety of confounding variables within a particular trial. More recent reports have confirmed that adjuvant radiotherapy will reduce the risk of local recurrence and in tumours of <5 cm with involved nodes, produce a reduction in breast cancer deaths. Improvements in breast cancer mortality may however be counterbalanced by increases in cardiac events and deaths caused by second malignancies. This stresses the importance of using megavoltage irradiation and avoiding excess cardiac doses particularly when treating left-sided tumours. Adjuvant radiotherapy combined with tamoxifen has been shown to produce an improvement in both local control and survival in postmenopausal node-positive patients who have undergone mastectomy. Adjuvant radiation combined with systemic chemotherapy has a significant effect on local recurrence and probably on survival in node-positive patients after mastectomy. There is little controversy over its role in patients with tumours >5 cm, with more than four nodes involved or with one to three nodes with extracapsular extension, or in those in whom axillary surgery has been deemed inadequate (i.e. <10 nodes). Debate still exists concerning T1/T2, G1/G2 tumours with only one to three nodes involved when the axillary surgery has been satisfactory (>10 nodes). The ongoing Intergroup trial may answer this question but until then other factors such as tumour grade and the presence of lymphovascular invasion can be included in the equation to determine which of the patients in the latter group should receive postoperative radiotherapy. Controversy still exists about what fields should be irradiated and in particular whether the supraclavicular fossa and internal mammary node chain should be included in adjuvant therapy. The EORTC is presently conducting a randomized trial, which should give us the answer. Treatment at relapse on the chest wall may require a combination of surgery, radiotherapy and chemotherapy, depending on previous therapy. If radiotherapy has not previously been used, then wide-field irradiation should be administered, including both chest wall and supraclavicular fossa with or without the axilla, depending on the extent of previous axillary surgery and the risk of lymphoedema. Re-irradiation after radical adjuvant radiotherapy can be considered only for selected patients when an adequate discussion with them has taken place with regard to the relative benefits versus toxicity.