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Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)–negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and location of ILRR. Patients with hormone receptor–positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti–human epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS), overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER-positive ILRR ( Pinteraction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and 0.94 (95% CI, 0.47 to 1.85), respectively, for breast cancer-free interval ( Pinteraction = .034) and 0.48 (95% CI, 0.19 to 1.20) and 0.70 (95% CI, 0.32 to 1.55), respectively, for overall survival ( Pinteraction = .53). Results for the three end points were consistent in multivariable analyses adjusting for location of ILRR, prior CT, and interval from primary surgery. Conclusion The final analysis of CALOR confirms that CT benefits patients with resected ER-negative ILRR and does not support the use of CT for ER-positive ILRR.

Summary Background Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. Methods The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti- HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. Findings From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6–6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56–79) with chemotherapy versus 57% (44–67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35–0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (p interaction =0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (p interaction =0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Interpretation Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. Funding US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Espanol de Investigacion en Cancer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

Background: Due to the rising trend of delaying pregnancy to later in life, more women are diagnosed with breast cancer before completing their families. Therefore, enquiry into the feasibility and safety of pregnancy following breast cancer diagnosis is on the rise. Available evidence suggests that women with a history of breast cancer are frequently advised against future conception for fear that pregnancy could adversely affect their breast cancer outcome. Hence, we conducted a meta-analysis to understand the effect of pregnancy on overall survival of women with a history of breast cancer. Methods: Two of the authors independently performed a literature search up to September 2009 with no language restrictions. Eligible studies were published retrospective control-matched, population-based and hospital-based studies that have addressed the impact of pregnancy on the overall survival of women with history of breast cancer. Pooling of data was done using the random effect model. Unpublished statistics from three studies were obtained to perform further subgroup and sensitivity analyses. This included examining the effect of pregnancy according to age at diagnosis, healthy mother effect, type of study, nodal status and other parameters. Results: Fourteen studies were included in this meta-analysis (1244 cases and 18,145 controls). Women who got pregnant following breast cancer diagnosis had a 41% reduced risk of death compared to women who did not get pregnant [PRR: 0.59 (90% confidence interval (CI): 0.50-0.70)]. This difference was seen irrespective of the type of the study and particularly in women with history of node-negative disease. In a subgroup analysis, we compared the outcome of women with history of breast cancer who became pregnant to breast cancer patients who did not get pregnant and were known to be free of relapse. In this analysis, we did not find significant differences in survival between either group [PRR: 0.85; 95% CI: 0.53-1.35]. Conclusions: This study confirms that pregnancy in women with history of breast cancer is safe and does not compromise their overall survival. Hence, breast cancer survivors should not be denied the opportunity of future conception. © 2010 Elsevier Ltd. All rights reserved. 47 1 74 83

To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.