2011 Lancet乳腺癌术后化疗

Comment Published online October 20, 2011 DOI:10.1016/S0140-6736(11)61296-8 1Radiotherapy and survival in breast cancerNearly 11 000 patients with early-stage breast cancer treated with breast-conserving surgery have participated in prospective phase 3 trials assessing the benefi ts of postoperative radiation to the breast. In The Lancet , the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) update their meta-analysis of long-term outcome in these patients.1 They report that radiotherapy leads to signifi cant clinical benefi ts, with an overall 16% absolute decrease (19% vs 35%) in the risk of breast cancer recurrence and a 4% absolute decrease (21% vs 25%, p<0·0001) in the risk of dying from breast cancer. These results confi rm that radiation is eff ective in eradication of much of the microscopic locoregional disease that might still be present after surgery. They also show that if radiation is not used, this persistent locoregional disease can metastasise and increase the chance of dying from breast cancer.The relation between locoregional treatments and death from breast cancer is complex. If the survival benefi ts with radiation are attributable to eradication of disease within the treatment volume, then for radiation to aff ect survival there are three conditions that must be met. First, patients must have disease in the locoregional area that has not been eradicated by surgery and will not be eradicated by adjuvant systemic treatments. Second, radiation must be successful in eradication of this disease. Third, patients must not have pre-existing distant micrometastatic disease, such as in lung, liver, or bone, that survives adjuvant systemic treatments. The EBCTCG data provide insight into eachof these three conditions.With respect to the fi rst issue, fi ndings from theEBCTCG meta-analysis clearly show that patients withbreast cancer have clinically relevant rates of persistentlocoregional disease after conservation surgery with andwithout systemic treatments. The magnitude of thisrisk is dependent on several factors, including axillarylymph-node status, tumour size, tumour grade, age,and oestrogen-receptor (ER) status. The analysis showsthat radiation is highly successful in eradication ofmuch of this disease. Previous analyses from this grouphave shown that the proportional reduction in isolatedlocoregional recurrence associated with radiation use is65–75%.2 In the latest EBCTCG study, the investigatorsstudied the eff ects of radiation on overall recurrence(locoregional recurrence or distant metastasis) and showed that radiotherapy led to a 50% proportional reduction in overall recurrence.1 To put this benefi t into context, a 50% proportional reduction in 10-year recurrence exceeds that from chemotherapy alone or hormonal therapy alone, and is roughly equivalent to the benefi ts of trastuzumab for patients with HER2/neu-positive disease.3–5 The latest analysis also shows that the success of radiation in reduction of recurrence varies according to biological subtype of breast cancer. In the EBCTCG study, the proportional reduction in risk of recurrence with radiation was nearly 60% for ER-positive disease treated with tamoxifen, but only 35% for ER-negative disease.1 Other investigators have shown that radiation achieves a greater reduction in locoregional recurrences for patients with ER-positive tumours than for those with ER-negative or triple-negative disease.6–9 These insights suggest that intensifi cation of locoregional treatment should be studied for ER-negative disease.The third factor important to the relation between radiation and survival is the risk of micrometastatic disease that can be present at a distant site at the time of locoregional treatment. The EBCTCG investigators suggest that for every four recurrences avoided by year 10, approximately one breast cancer death is avoided by year 15. These investigators reported this same 4:1 relation in a previous meta-analysis of trials assessing postmastectomy radiotherapy.2 Together, Published Online October 20, 2011DOI:10.1016/S0140-6736(11)61296-8See Online/ArticlesDOI:10.1016/S0140-6736(11)61629-2S c i e n c e P h o t o L i b r a r yComment2 Published online October 20, 2011 DOI:10.1016/S0140-6736(11)61296-8these data can be interpreted as suggesting that most patients who had persistent locoregional disease eradicated by radiation had micrometastases at a remote site at the time of treatment or had successful salvage of a locoregional recurrence. The 4:1 relation might be an oversimplifi cation, and the relation between locoregional recurrence prevention and avoidance of death probably changes across various stages of disease and type of surgery. For example, patients with supraclavicular lymph-node involvement and those with multiple positive lymph nodes after a course of neoadjuvant chemotherapy and mastectomy have very high risk of locoregional recurrence and therefore have large absolute improvements in locoregional recurrences with adjuvant radiation treatment. Unfortunately, such patients also have very high competing risks of distant metastases, and the salvage rates of locoregional recurrences are fairly low. Therefore, the large absolute benefi ts in locoregional recurrences in such patients might not translate into a large overall survival benefi t. The Danish 82b and 82c trials 10 have provided additional insights into the relation between locoregional control and survival in patients treated with mastectomy. The Danish data suggest that patients with favourable disease characteristics, such as a low number of positive lymph nodes and ER-positive disease, have the greatest survival benefi t from locoregional recurrence prevention.The data from many thousands of clinical trial patients reviewed by the EBCTCG investigators continue to provide us with crucially important insights. The data reinforce the important role that radiotherapy has in management of breast cancer, and the fact that the benefi ts of radiation are complementary to the advances in both surgery and systemic treatment is particularly rewarding. The incremental benefi ts of each component of treatment contribute to the ongoing success in reduction of breast cancer mortality rates.Thomas A Buchholz The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA tbuchhol@ I declare that I have no confl icts of interest.1 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Eff ect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet 2011; published online Oct 20. DOI:10.1016/S0140-6736(11)61629-2.2 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Eff ects of radiotherapy and of diff erences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366: 2087–106.3 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Eff ects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–717.4 Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353: 1659–72.5 Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353: 1673–84.6 Kyndi M, Sorensen FB, Knudsen H, Overgaard M, Nielsen HM, Overgaard J. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol 2008; 26: 1419–26.7 Nguyen PL, Taghian AG, Katz MS, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 2008; 26: 2373–78.8 Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 2010; 28: 1684–91.9 Woodward WA, Strom EA, Tucker SL, et al. Locoregional recurrence after doxorubicin-based chemotherapy and postmastectomy: implications for breast cancer patients with early-stage disease and predictors for recurrence after postmastectomy radiation. Int J Radiat Oncol Biol Phys 2003; 57: 336–44.10 Kyndi M, Overgaard M, Nielsen HM, Sorensen FB, Knudsen H, Overgaard J. High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol 2009; 90: 74–79.。