Life events and breast cancer prognosis.

OBJECTIVE--To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN--Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING--Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS--204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES--Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS--After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION--These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.     

Stressful life experiences and risk of relapse of breast cancer: observational cohort study

ObjectiveTo confirm, using an observational cohort design, the relation between severely stressful life experiences and relapse of breast cancer found in a previous case-control study.DesignProspective follow up for five years of a cohort of women newly diagnosed as having breast cancer, collecting data on stressful life experiences, depression, and biological prognostic factors.SettingNHS breast clinic, London; 1991-9.ParticipantsA consecutive series of women aged under 60 newly diagnosed as having a primary operable breast tumour. 202/222 (91%) eligible women participated in the first life experiences interview. 170 (77%) provided complete interview data either up to 5 years after diagnosis or to recurrence.ResultsWe controlled for biological prognostic factors (lymph node infiltration and tumour histology), and found no increased risk of recurrence in women who had had one or more severely stressful life experiences in the year before diagnosis compared with women who did not (hazard ratio 1.01, 95% confidence interval 0.58 to 1.74, P=0.99). Women who had had one or more severely stressful life experiences in the 5 years after diagnosis had a lower risk of recurrence (0.52, 0.29 to 0.95, P=0.03) than those who did not.ConclusionThese data do not confirm an earlier finding from a case-control study that severely stressful life experiences increase the risk of recurrence of breast cancer. Differences in case control and prospective methods may explain the contradictory results. We took the prospective study as the more robust, and the results suggest that women with breast cancer need not fear that stressful experiences will precipitate the return of their disease.

What is already known on this topic

Women with apparently similar tumours at the time of presentation with breast cancer differ considerably in their disease-free survival and overall survivalSuch differences in outcome may well be explained by host and environmental factors, which could include psychological and social variablesData on the relation between severely stressful life experiences and cancer progression have been contradictory

What this study adds

Women who have a severely stressful life experience in the year before being diagnosed with breast cancer, or in the five years afterwards, do not seem to be at increased risk of developing a recurrence of the diseaseWomen with breast cancer need not fear that stressful experiences will precipitate the return of their disease.     

Adverse life events and breast cancer: case-control study.

OBJECTIVE--To investigate the strength of association between past life events and the development of breast cancer. DESIGN--Case-control study. A standardised life events interview and rating was administered before a definitive diagnosis. SETTING--Breast Cancer Screening Assessment Unit and surgical outpatient clinics at King''s College Hospital, London. SUBJECTS--119 consecutive women aged 20-70 who were referred for biopsy of a suspicious breast lesion. MAIN OUTCOME MEASURES--Odds ratio of the risk of developing breast cancer after life events in the preceding five years after adjustment for confounders. RESULTS--41 women were diagnosed as having malignant disease while the remainder had benign conditions. Severe life events increased the risk of breast cancer. The crude odds ratio was 3.2 (95% confidence interval 1.35 to 7.6). After adjustment for age and the menopause and other potential confounders this rose to 11.6 (3.1 to 43.7). Multiple logistic regression analysis showed that all severe events and coping with the stress of adverse events by confronting them and focusing on the problems significantly predicted a diagnosis of breast cancer. Non-severe life events and long term difficulties had no significant association. CONCLUSION--These findings suggest an aetiological association between life stress and breast cancer.     

Stressful life events and difficulties and onset of breast cancer: case-control study

ObjectiveTo determine the relation between stressful life events and difficulties and the onset of breast cancer.DesignCase-control study.Setting3 NHS breast clinics serving west Leeds.Participants399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents.Results332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1.81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump.ConclusionThese findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.

Key messages

• Although there is widespread belief that stress can cause cancer, research evidence is contradictory
• Stressful life experiences are common; about two thirds of women with a breast lump experienced at least one severe life event or difficulty in the 5 years before presentation
• Women diagnosed with breast cancer were no more likely to have experienced a severe stressor than women with a benign lesion
• Knowledge or suspicion of the diagnosis did not influence reporting of severe life events

     

Risk factors for breast cancer in women biopsied for benign breast disease: A nested case-control study

Aim: Women with a history of benign breast disease are at increased risk of subsequent breast cancer. However, few studies have examined whether established breast cancer risk factors other than histology are associated with an altered risk of breast cancer in women with benign breast disease. We used a nested case-control design within a large, multi-center cohort of women biopsied for benign breast disease (BBD) to estimate odds ratios for breast cancer in association with exposure to a range of personal and lifestyle factors. Methods: Cases were women biopsied for BBD who subsequently developed breast cancer; controls were individually matched to cases on center and age at diagnosis and were women biopsied for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After excluding women with prevalent breast cancer, 1357 records (661 case records and 696 records) were available for analysis. We used conditional logistic regression to obtain crude and multivariable-adjusted estimates of the association between specific factors and risk of breast cancer. Results: In multivariable analyses age at first live birth, number of pregnancies, and postmenopausal status were inversely associated with risk of breast cancer. The odds ratio for women with age at first birth <25 years and ≥3 pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval 0.13–0.79, and that for postmenopausal women relative to premenopausal women was 0.60, 95% CI 0.37–0.99. Conclusions: Further study of personal factors influencing the risk of breast cancer in women with BBD may help to identify subgroups of the population at increased risk of invasive disease.     

Prognostic significance of plasminogen activator inhibitor-1 in breast cancer, with special emphasis on locoregional recurrence-free survival

The independent prognostic value of protease uPA and its inhibitor PAI-1 for survival in breast cancer patients is firmly established. However, there is very little data on the prognostic value of serine proteases and their inhibitors for locoregional recurrence in breast cancer. The prognostic value of PAI-1 for local control in a group of 766 patients treated at our institute with either breast conserving treatment or modified radical mastectomy was evaluated. The locoregional recurrence-free survival (LRFS) of patients with PAI-1 values above the median value was significantly worse than that of patients with PAI-1 values below the median value (log-rank; p=0.0078). In multivariate analysis PAI-1 levels proved to be of independent statistical significance for LRFS (p=0.0401, relative risk 2.28, 95% confidence interval 1.04-5.02). The independent prognostic value of PAI-1 for metastasis-free survival and overall survival was also confirmed. In addition, our data suggest that PAI-1 antigen levels in tumor tissue might be of prognostic value for survival after locoregional recurrence (log-rank; p=0.0618). According to our findings, PAI-1 levels could be used as a biological marker that could facilitate the identifation of patients with a higher risk of local relapse already at the time of primary treatment. These patients should then be offered more aggressive treatment.     

Breast implants and cancer: causation, delayed detection, and survival

Concern for many women with breast implants has been focused on three topics: cancer (both breast and other cancers), delayed detection of breast cancer, and increased breast cancer recurrence or decreased length of survival. In this study, a qualitative review of the literature on these subjects was conducted, coupled with a meta-analysis of the risk for breast cancer or other cancers (excluding that of the breast). Researchers have consistently found no persuasive evidence of a causal association between breast implants and any type of cancer. The meta-analysis results obtained by combining the epidemiology studies support the overall conclusion that breast implants do not pose any additional risk for breast cancer (relative risk, 0.72; 95% confidence interval, 0.61 to 0.85) or for other cancers (relative risk, 1.03; 95% confidence interval, 0.87 to 1.24). This analysis suggests that breast implants may confer a protective effect against breast cancer. Women with implants should be reassured by the consistency of scientific studies which have uniformly determined that, compared with women without implants, they are not at increased risk for cancer, are not diagnosed with later-stage breast malignancies, are not at increased risk for breast cancer recurrence, and do not have a decreased length of survival.     

Immune, endocrine, and behavioral precursors to breast cancer recurrence: a case-control analysis

BACKGROUND: A period of tumor growth precedes the clinical detection of breast cancer recurrence. We explore immune, endocrine, and behavioral parameters during this period. METHODS: We conducted a phase III clinical trial in which women with surgically treated stage II/III breast cancer (N = 227) were randomized to receive a psychological intervention or assessment-only and then regularly assessed for 10 years. Patients who recurred (R, n = 48) were matched with patients remaining disease-free (DF, n = 48) on demographic and prognostic characteristics, treatment, and duration of disease-free follow-up. Data at three assessment points, occurring, on average, 17, 11, and 4 months before the recurrence was detected clinically, with equivalent time points for the disease-free group, were examined. Mixed-effects models tested for group differences in immune cell counts and function as well as endocrine and behavioral parameters. RESULTS: In the 17 months prior to recurrence detection, patients exhibited higher white blood cell count, neutrophil, lymphocyte, and natural killer cell counts, relative to DF patients. R patients also showed higher cortisol, worse physical functioning, fatigue, and quality of life. Follow-up analyses showed patients with local recurrences to differ from those with distant recurrence, with the former exhibiting elevated natural killer cell cytotoxicity, lymphocyte proliferative response, fatigue, pain, and emotional distress (depression, anxiety), and the latter exhibiting higher neutrophil, lymphocyte, and natural killer cell counts. CONCLUSION: Patients who would recur showed reliable biobehavioral alterations more than a year prior to their diagnosis. This novel observation may contribute to our understanding of the disease relapse processes.     

Depot medroxyprogesterone (Depo-Provera) and risk of breast cancer.

OBJECTIVE--To determine whether use of the injectable contraceptive depot medroxyprogesterone acetate (Depo-Provera) affects the risk of breast cancer in women. DESIGN--A population based case-control study. SETTING--Nationwide community study. SUBJECTS--891 Women aged 25-54 with newly diagnosed breast cancer were compared with 1864 women selected at random from the electoral rolls. INTERVENTION--Women were interviewed by telephone about past use of contraceptives and about possible risk factors for breast cancer. MAIN OUTCOME MEASURE--Relative risk of breast cancer in women who had used medroxyprogesterone. RESULTS--Medroxyprogesterone had been used by 110 patients and 252 controls. Overall, the relative risk of breast cancer associated with any duration of use was 1.0 (95% confidence interval 0.80 to 1.3). In women aged 25-34 the relative risk was 2.0 (1.0 to 3.8). The relative risk was highest in women aged 25-34 who had used the drug for six years or longer, although there were few women in this category. Women who had used it for two years or longer before age 25 had an increased risk of breast cancer (relative risk 4.6; 1.4 to 15.1). CONCLUSION--Despite the lack of an overall association these findings suggest that medroxyprogesterone may increase the risk of breast cancer in young women.     

An estrogen receptor (ER)‐related signature in predicting prognosis of ER‐positive breast cancer following endocrine treatment

Quite a few estrogen receptor (ER)‐positive breast cancer patients receiving endocrine therapy are at risk of disease recurrence and death. ER‐related genes are involved in the progression and chemoresistance of breast cancer. In this study, we identified an ER‐related gene signature that can predict the prognosis of ER‐positive breast cancer patient receiving endocrine therapy. We collected RNA expression profiling from Gene Expression Omnibus database. An ER‐related signature was developed to separate patients into high‐risk and low‐risk groups. Patients in the low‐risk group had significantly better survival than those in the high‐risk group. ROC analysis indicated that this signature exhibited good diagnostic efficiency for the 1‐, 3‐ and 5‐year disease‐relapse events. Moreover, multivariate Cox regression analysis demonstrated that the ER‐related signature was an independent risk factor when adjusting for several clinical signatures. The prognostic value of this signature was validated in the validation sets. In addition, a nomogram was built and the calibration plots analysis indicated the good performance of this nomogram. In conclusion, combining with ER status, our results demonstrated that the ER‐related prognostic signature is a promising method for predicting the prognosis of ER‐positive breast cancer patients receiving endocrine therapy.     

Breast-conservation treatment for early invasive breast cancer: prognostic factors for survival after salvage treatment of local recurrence

The aim of the study was to investigate prognosis of patients who develop an isolated local recurrence (ILR) after conservative surgery (CS) for early-stage invasive breast cancer. Between 1983 and 1987, 415 patients with stage I-II breast cancer were treated with CS. Of these patients, 68 developed an ILR. The mean follow-up time after ILR was 167 months. Cox models taking potential prognostic factors into account were used to estimate the risk of death. On univariate analysis, age (< or =40 vs. >40 years) at first treatment, time to ILR (< or =24 vs. >24 months), type of recurrence (true vs. new primary tumor, NP), and extent of recurrence (operable vs. inoperable) were, but initial tumor stage (pT1 vs. pT2), initial lymph node stage (pN-negative vs. -positive), adjuvant radiotherapy (yes vs. no), type of salvage surgery (wide excision vs. mastectomy), and recurrent tumor grade (1-2 vs. 3) were not significant predictors of post-recurrence survival. On multivariate analysis only time to ILR proved independent predictor of survival (relative risk: 3.2; 95% confidence interval: 1.4-7.3; p = 0.0051), and the age of the patients showed borderline significance (p = 0.0659). The 15-year actuarial rate of cause-specific survival after ILR was 58% for all patients, 60% and 0% for patients with operable or inoperable recurrence, 30% and 71% for patients with age < or =40 or >40 years, 25% and 72% for patients with time to ILR < or =24 or >24 months, 54% and 88% for patients with true recurrence or NP, and 92% for patients with age >40 years with NP, respectively. The rate of second local recurrence after salvage mastectomy or repeated wide excision was 16% and 28%, respectively (p = 0.2265). As a conclusion, many patients with ILR have good prognosis, particularly those with operable recurrence with prolonged time to ILR, or with NP. Salvage mastectomy is not mandatory for all CS patients.     

Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer.

OBJECTIVE--To identify any excess mortality caused by adjuvant radiotherapy for early breast cancer. DESIGN--Prospective randomised clinical trial. Two thousand subjects needed for study to have a 90% chance of detecting a difference in survival rate of 7% with 95% significance. Patients were followed up until June 1988, giving follow up of 158-216 months. SETTING--A multicentre trial mainly drawing patients from centres in the United Kingdom. PATIENTS--2800 Women presenting with clinical stage I or II carcinoma of the breast from June 1970 to April 1975. INTERVENTIONS--One group of women (n = 1376) had simple mastectomy followed by immediate postoperative radiotherapy (1320 to 1510 rets). The remaining women (n = 1424) had simple mastectomy with subsequent careful observation of the axilla, radiotherapy being delayed until there was obvious progression or recurrence of disease locally. END POINT--Increased mortality in patients treated with radiotherapy from causes other than breast cancer. MEASUREMENTS AND MAIN RESULTS--Survival was measured from time of first treatment to death or last follow up. Deaths from any cause and from specified causes were counted as events. Comparison over the whole follow up showed a slight excess mortality in the group treated with radiotherapy (relative risk 1.04; 95% confidence interval 0.94 to 1.15). The relative risk of death from breast cancer was 0.97 (0.87 to 1.08) but that of death from other causes was 1.37 (1.09 to 1.72), the increase mainly being in women who had had tumours of the left breast (1.61 (1.17 to 2.24)) and had been treated with orthovoltage (1.85 (1.27 to 2.71)). Analysis of causes of death after five years showed a relative risk of 2.11 (1.25 to 3.59) for new malignancies and of 1.65 (1.05 to 2.58) for cardiac disease, the increase in cardiac mortality being most pronounced in patients who had had tumours of the left breast and whose treatment had included orthovoltage radiation (relative risk 2.67 (1.28 to 5.55)). CONCLUSIONS--Adjuvant radiotherapy after simple mastectomy for early breast cancer produces a small excess late mortality from other cancers and cardiac disease. The risk has to be balanced against the higher risk of local recurrence when immediate postoperative radiotherapy is not given. The balance has to be assessed for each patient, and for many patients radiotherapy will still be desirable in the initial treatment of their early breast cancer.     

Time since childbirth and prognosis in primary breast cancer: population based study.

OBJECTIVE: To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. DESIGN: Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. SETTING: Denmark. SUBJECTS: 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. MAIN OUTCOME MEASURES: 5 and 10 year survival; relative risk of dying. RESULTS: Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. CONCLUSIONS: A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.     

Prognostic factors for early relapse in non-metastatic triple negative breast cancer — real world data

BackgroundTriple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse.Materials and methodsSingle-centre retrospective analysis of 127 women with TNBC, stage II–III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse.ResultsAfter 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3–22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2–6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1–1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively).ConclusionsIn this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.     

Breast cancer risk and the interaction between adolescent body size and weight gain in later life: A case-control study

BackgroundWhile the breast cancer risk associated with increasing adult BMI in postmenopausal women can be explained by increases in concentrations of endogenous estrogens the biologic mechanisms behind the inverse association between adolescent BMI and breast cancer risk are still a subject of controversial debate.MethodsWe investigated the association of breast cancer with body size and changes in body size across life time estimated by age-specific BMI Z scores and changes in BMI Z scores from teenage years to middle age in an age-matched population-based case-control study of 2994 Australian women. Logistic regression adjusted for the matching factor age and further potential confounders was used.ResultsAdolescent body leanness in postmenopausal women and excess adult weight gain in all study participants were associated with an increased breast cancer risk with an odds ratio [95% confidence interval] of 1.29 [1.08,1.54] and 1.31 [1.09,1.59], respectively. Interaction analyses restricted to postmenopausal women revealed an increased risk of breast cancer in those who were lean during adolescence and gained excess weight during adulthood (odds ratio [95% confidence interval]: 1.52 [1.19,1.95]) but not in women who were lean during adolescence and did not gain excess weight during adulthood (1.20 [0.97,1.48]) and not in women who were not lean during adolescence and but gained excess weight during adulthood (1.10 [0.95,1.27]) compared to postmenopausal women who were neither lean during adolescence nor gained excess weight.ConclusionIn postmenopausal women adolescent leanness was only associated with increased breast cancer risk when excess weight was gained during adulthood.     

Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee.

OBJECTIVE--To investigate the incidence of fatal myocardial infarction in women in the two randomised arms of the Scottish adjuvant tamoxifen trial. DESIGN--Retrospective review of hospital notes to determine with the greatest possible certainty women who had died of an acute myocardial infarction. SETTING--Scottish Cancer Trials Office, the University of Edinburgh. PATIENTS--1070 postmenopausal women with operable breast cancer who were randomised to receive either adjuvant tamoxifen for five years or until relapse (539 patients) or tamoxifen for at least six weeks on the confirmation of first recurrence (531 patients). MAIN OUTCOME MEASURES--Incidence of fatal myocardial infarction in women with no known or suspected systemic cancer. RESULTS--Of the 200 women who died in the adjuvant tamoxifen arm of the trial, 44 were free of cancer at death and 10 of these died of myocardial infarction. In the observation arm 251 women died, of whom 61 showed no evidence of systemic cancer and 25 had a fatal myocardial infarction. The incidence of fatal myocardial infarction in the two groups was significantly different (chi 2 = 6.88, p = 0.0087). CONCLUSION--Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women.     

Clinical practice guidelines for the care and treatment of breast cancer: 14. The role of hormone replacement therapy in women with a previous diagnosis of breast cancer

Objective

To provide information and recommendations to women with a previous diagnosis of breast cancer and their physicians regarding hormone replacement therapy (HRT).

Outcomes

Control of menopausal symptoms, quality of life, prevention of osteoporosis, prevention of cardiovascular disease, risk of recurrence of breast cancer, risk of death from breast cancer.

Evidence

Systematic review of English-language literature published from January 1990 to July 2001 retrieved from MEDLINE and CANCERLIT.

Recommendations

· Routine use of HRT (either estrogen alone or estrogen plus progesterone) is not recommended for women who have had breast cancer. Randomized controlled trials are required to guide recommendations for this group of women. Women who have had breast cancer are at risk of recurrence and contralateral breast cancer. The potential effect of HRT on these outcomes in women with breast cancer has not been determined in methodologically sound studies. However, in animal and in vitro studies, the development and growth of breast cancer is known to be estrogen dependent. Given the demonstrated increased risk of breast cancer associated with HRT in women without a diagnosis of breast cancer, it is possible that the risk of recurrence and contralateral breast cancer associated with HRT in women with breast cancer could be of a similar magnitude. · Postmenopausal women with a previous diagnosis of breast cancer who request HRT should be encouraged to consider alternatives to HRT. If menopausal symptoms are particularly troublesome and do not respond to alternative approaches, a well-informed woman may choose to use HRT to control these symptoms after discussing the risks with her physician. In these circumstances, both the dose and the duration of treatment should be minimized.

Validation

Internal validation within the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer; no external validation.

Sponsor

The steering committee was convened by Health Canada.

Completion date

October 2001.Hormone replacement therapy (HRT) connotes treatment with either estrogen alone or estrogen with progesterone in postmenopausal women. Menopausal symptoms, such as hot flashes and vaginal dryness, and the potential long-term effects of estrogen deprivation are a concern to women with breast cancer, particularly those in whom menopause develops early as a result of adjuvant chemotherapy.Traditionally, the use of HRT has been contraindicated in women with breast cancer because of the notion that the development and growth of breast cancer is estrogen dependent and that the introduction of HRT may increase the risk of breast cancer recurrence. The focus of this guideline is on whether it is safe to give HRT to women with breast cancer.     

Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients

Background

Taxanes have been extensively used as adjuvant chemotherapy for the treatment of early or operable breast cancer, particularly in high risk, node-negative breast cancer. Previous studies, however, have reported inconsistent findings regarding their clinical efficacy and safety. We investigated disease-free survival (DFS), overall survival (OS), and drug-related toxicities of taxanes by a systematic review and meta-analysis.

Methodology and Principal Findings

We systematically searched PubMed, EMBASE, the Cochrane Center Register of Controlled Trials, proceedings of major meetings, and reference lists of articles for studies conducted between January 1980 and April 2011. Randomized controlled trials (RCTs) comparing chemotherapy with and without taxanes in the treatment of patients with early-stage or operable breast cancer were eligible for inclusion in our analysis. The primary endpoint was DFS. Nineteen RCTs including 30698 patients were identified, including 8426 recurrence events and 3803 deaths. Taxanes administration yielded a 17% reduction of hazard ratio (HR) for DFS (HR = 0.83, 95% CI 0.79–0.88, p<0.001) and a 17% reduction of HR for OS (HR = 0.83, 95% CI 0.77–0.90, p<0.001). For high risk, node-negative breast cancer, the pooled HR also favoured the taxane-based treatment arm over the taxane-free treatment arm (HR = 0.82, 95% CI 0.77–0.87, p = 0.022). A significantly increased rate of neutropenia, febrile neutropenia, fatigue, diarrhea, stomatitis, and oedema was observed in the taxane-based treatment arm.

Conclusions/Significance

Adjuvant chemotherapy with taxanes could reduce the risk of cancer recurrence and death in patients with early or operable breast cancer, although the drug-related toxicities should be balanced. Furthermore, we also demonstrated that patients with high risk, node-negative breast cancer also benefited from taxanes therapy, a result that was not observed in previous studies.     

Breast feeding and risk of breast cancer in young women. United Kingdom National Case-Control Study Group.

OBJECTIVE--To investigate whether breast feeding is related to subsequent risk of breast cancer. DESIGN--Population based case-control study designed primarily to investigate the relation between oral contraceptives and risk of breast cancer; data obtained from questionnaires administered by interviewers, general practitioner notes, and family planning clinic records. SETTING--11 health regions in Britain. SUBJECTS--Women diagnosed with breast cancer before age 36 living in the defined study areas. One control per case, matched for age, was selected from the list of the case''s general practitioner. 755 case-control pairs were interviewed. MAIN OUTCOME MEASURES--Duration of breast feeding each liveborn infant; timing of return of menses; hormone use; other risk factors for breast cancer. RESULTS--Risk of breast cancer fell with increasing duration of breast feeding (relative risk = 0.94 per three months'' breast feeding; test for trend p = 0.026) and with number of babies breast fed (relative risk = 0.86; test for trend, p = 0.017). Breast feeding each baby for longer than three months conferred no additional benefit. Breast feeding was more strongly negatively associated with risk of breast cancer than duration of postpartum amenorrhoea (chi 2 test for trend, p = 0.69). Hormonal suppression of lactation was unrelated to risk of breast cancer (relative risk = 0.96 per episode of suppressed lactation; test for trend, p = 0.72). CONCLUSIONS--These results suggest that breast feeding protects against the development of breast cancer in young women.