SummaryBackgroundFor women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years.MethodsIn the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633.FindingsAmong women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%).InterpretationFor women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurren...
The study aims to evaluate the survival and prognosis of patients with malignant phyllodes tumor. Between 1982 and 1998, 37 women with malignant phyllodes tumor were treated at the Regional Cancer Center, Trivandrum. Twelve patients were recurrent. Survival was estimated using the Kaplan-Meier method. Patient, disease, and treatment factors were compared using log-rank test. The Cox-proportional hazard model was employed to identify the prognostic factors. Thirty-six patients had surgery. Twenty-five patients received postoperative radiotherapy, and 2 received chemotherapy in addition. The median follow-up was 43 months (range 1-170 months). Eight patients failed locally, and 7 of these were successfully salvaged by surgery. The 5-year overall survival was 74.2% (95% CI, 0.44 to 0.89), whereas 5-year disease-free survival was 59.6% (95% CI, 0.39 to 0.7). The margin of surgical excision was found to be the only independent prognostic factor (p=0.003). However, patients with tumor size more than 5 cm (hazard ratio 2.9) were found to have increased hazard, whereas those receiving adjuvant radiotherapy (hazard ratio 0.6), married women (hazard ratio 0.4), and those women over the age of 35 years (hazard ratio 0.7) showed a decreased hazards. Cystosarcoma phyllodes is a rare malignancy of the female breast. Surgery with adequate margins is the primary treatment. Adjuvant radiotherapy appears to improve the disease-free survival.
X-ray repair cross-complementing 1 (XRCC1) gene encodes for a scaffolding protein, which plays an important role in base excision DNA repair by bringing together DNA polymerase beta, DNA ligase III and poly(ADP-Ribose) polymerase (PARP) at the site of DNA damage. Three polymorphisms of the XRCC1 gene at codons 194, 280 and 399 leading to amino acid changes at evolutionary conserved regions are found to alter the efficiency of the resulting protein and may therefore constitute potential breast cancer risk. In the present study we sought to determine whether these genetic variants of the XRCC1 gene was associated with any increased risk of breast cancer among the South Indian women in a hospital based case control study using PCR-RFLP and DNA sequencing techniques. Our data showed a positive association between the polymorphisms of codons 194 (OR = 1.98, 95% CI = 1.13-3.48 for Trp allele) and 399 (OR = 2.14, 95% CI = 1.29-3.58 for Gln allele) and breast cancer risk. However, XRCC1 codon 280 genotype analysis showed no evidence for an association with increased risk of breast cancer. A combined analysis of the effect of XRCC1 codon 194 and 399 revealed the highest risk (OR = 3.64, 95% CI = 1.57-8.46) for carriers of the polymorphic alleles in both these codons. In conclusion, the present study suggested involvement of XRCC1 codon 194 and 399 polymorphisms in the genetic predisposition to breast cancer among South Indian women. Our preliminary results based on the analysis of functionally relevant polymorphisms in XRCC1 low penetrance gene may provide a better model that would exhibit additive effects on individual susceptibility to breast cancer.
Breast cancer incidence is low in India compared with highincome countries, but it has increased in recent decades, particularly among urban women. The reasons for this pattern are not known although they are likely related to reproductive and lifestyle factors. Here, we report the results of a large case-control study on the association between breastfeeding and breast cancer risk. The study was conducted in 2 areas in South India during [2002][2003][2004][2005] and included 1,866 cases and 1,873 controls. Detailed information regarding menstruation, reproduction, breastfeeding and physical activity was collected through in-person interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression models. Breastfeeding for long duration was common in the study population. Lifetime duration of breastfeeding was inversely associated with breast cancer risk among premenopausal women (p-value of linear trend, 0.02). No such protective effect was observed in postmenopausal women, among whom a protective effect of parity was suggested. A reduction of breast cancer risk with prolonged breastfeeding was shown among premenopausal women. Health campaign focusing on breastfeeding behavior by appropriately educating women would contribute to reduce breast cancer burden. ' UICCKey words: breastfeeding; breast cancer; India Breast cancer is the most common cancer in women worldwide with nearly 1,000,000 new cases each year, representing over 20% of all malignancies. 1 There are striking geographic variations in breast cancer incidence with more than a 10-fold difference between low rates in rural African and Asian populations and high rates in North American and Western European populations.Age-standardized breast cancer incidence rates in India range from 15 to 29 per 100,000 and have been increasing in recent decades, especially among urban women, and India is now the country with the largest estimated number of breast cancer deaths worldwide. 1 The reasons for the low incidence of breast cancer among Indian women and the increasing incidence in recent years are not completely understood, although are likely to be explained by reproductive and lifestyle factors. Only few epidemiological studies have been conducted to determine the risk factors of breast cancer in Indian women. [2][3][4] Although it is well established that prolonged breastfeeding decreases the risk of breast cancer, 5 most of the evidence derives from studies conducted in high-income countries. Data from lowincome countries, where prolonged breastfeeding is prevalent, are needed to better quantify the effect of long-term breastfeeding.The World Health Organization (WHO) 6 conducted a study on breastfeeding in India between 1975 and 1978, and found sociocultural factors such as education, employment and income to be the strongest determinants of the length of breastfeeding; 96% of mothers in the urban areas and 100% in rural areas breastfed their infants. Data from National Family Health Survey-2 show that in ...
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