To evaluate whether tumor androgen receptor (AR) expression was prognostic and/or predictive for endocrine treatment alone or in combination with estrogen receptor (ER). The AR has been hypothesized to have differential prognostic roles in breast cancer depending on tumor ER status, and to influence endocrine treatment response.
A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between 2002 and 2012 was followed until June 2014. Associations between immunohistochemical AR expression in tumor tissue microarrays, patient and tumor characteristics, and AR genotypes were analyzed. Disease-free survival (DFS) by AR status, and combined ER/AR status was assessed in various treatment groups.
AR expression was assessable in 913 tumors. AR(+) tumors (85.0%) were associated with higher age (P = 0.036) and favorable tumor characteristics. The AR(+) status was a prognostic marker for DFS (LogRank P = 0.025). There was an interaction between AR and ER expression with respect to prognosis (adjusted P(interaction) = 0.024). Tumors with discordant hormone receptor expressions (ER(+)AR(-) or ER(-)AR(+)) demonstrated worse prognosis compared with concordant tumor expressions (ER(+)AR(+) or ER(-)AR(-)) in multivariable models [adjusted HRs (95% confidence intervals); = 1.99 (1.28-3.10), P = 0.002]. ER(+)AR(-) indicated early treatment failure with aromatase inhibitors (AI) among chemonaïve patients aged 50 or older.
Prediction of breast cancer prognosis and treatment response was improved by combining AR and ER status. AR negativity predicted early treatment failure with AI but not tamoxifen, a finding that warrants confirmation in a randomized setting. Patients may benefit from anti-androgens or selective AR modulators.
A total of 266 recurrence-free breast cancer patients from the randomized DBCG-82TM breast conservation trial were called in for a follow-up investigation to study the impact of surgical and radiation treatment factors on the cosmetic and functional outcome after breast conservation. The patients were interviewed and examined after a median follow-up time of 6.6 years, and 194 of them (73%) regarded the cosmetic result as excellent or good. Morbidity assessments showed that breast fibrosis, skin telangiectasia, and breast retraction were significantly associated with a less satisfactory cosmetic result. On univariate analysis, it was found that treatment with a direct anterior electron field produced more morbidity and inferior cosmetic outcomes compared with tangential photon treatment, while increasing breast size was associated with increased breast retraction and breast fibrosis. Treatment characteristics that emerged as independent prognostic factors of a poor cosmetic outcome on multivariate analysis were the use of a direct anterior electron field (OR = 2.15, CI 1.25-3.70) and adjuvant systemic therapy (OR = 2.13, 1.22-3.71). A significant but relatively low level of concordance was found between the patients' and the clinician's evaluations of cosmetic results but self-assessments of breast morbidity and psychological distress were significantly related to the observed treatment-induced side effects after breast-conserving treatment, indicating that subjective perceptions and observations as reported by the patients are relevant for the identification of treatment factors that impact on normal tissue reactions.
Body mass index (BMI), waist-to-hip ratio (WHR), and tumor characteristics affect disease-free survival. Larger breast size may increase breast cancer risk, but its influence on disease-free survival is unclear. The purpose of this study was to elucidate whether breast size independently influenced disease-free survival in breast cancer patients.
Body measurements were obtained preoperatively from 772 breast cancer patients in a population-based ongoing cohort from southern Sweden. The research nurse measured breast volumes with plastic cups used by plastic surgeons doing breast reductions. Clinical data were obtained from patient charts and pathology reports.
Patients with a BMIÂ =Â 25Â kg/m(2) had larger tumors (pÂ Â 0.85 had larger tumors (pÂ =Â 0.013), more advanced histological grade (pÂ =Â 0.0016), and more axillary nodal involvement (pÂ =Â 0.012). Patients with rightÂ +Â left breast volumeÂ =Â 850Â mL were more likely to have larger tumor sizes (pÂ =Â 0.018), more advanced histological grade (pÂ =Â 0.031), and more axillary nodal involvement (pÂ =Â 0.025). There were 62 breast cancer events during the 7-year follow-up. Breast volumeÂ =Â 850Â mL was associated with shorter disease-free survival (pÂ =Â 0.004) and distant metastasis-free survival (pÂ =Â 0.001) in patients with estrogen receptor (ER)-positive tumors independent of other anthropometric measurements and age. In patients with ER-positive tumors, breast size was an independent predictor of shorter disease-free (HR 3.64; 95Â % CI 1.42-9.35) and distant metastasis-free survival (HR 6.33; 95Â %CI 1.36-29.43), adjusted for tumor characteristics, BMI, age, and treatment.
A simple and cheap anthropometric measurement with standardized tools may help identify a subgroup of patients in need of tailored breast cancer therapy.
Overweight and obesity are increasing worldwide, but the extent in breast cancer patients is unknown. The two aims were to study secular trends in preoperative body mass index (BMI), waist circumference, and breast volume and their impacts on clinical outcome. BMI, waist circumference, and breast volume were measured preoperatively in 24-99-year-old primary breast cancer patients (n?=?640) in Sweden 2002-2016. The measurements were analyzed alone and combined in relation to recurrence and overall survival (OS). BMI, waist circumference, and breast volume increased 2002-2016 (ptrends?
We have studied the use of complimentary alternative medicine (CAM) among 233 consecutive breast cancer patients operated on at the Lund University Hospital, Sweden between 2002 and 2004. Questionnaires were administered preoperatively (n = 233), and again 3-6 months post-operatively (n = 167) and one year after surgery (n = 88). At baseline, 14,5% used CAM, 3-6 months post-operatively 14,4% used CAM and one year after surgery 18,2% used CAM. The most common products contained omega-3, garlic, ginseng and roseroot. We identified use of 35 different types of CAM products and seven of these could potentially increase the risk of breast cancer or interact with tamoxifen or aromatase inhibitors: soy, garlic, ginko biloba, echinacea, ginseng, valerian and phytoestrogens (excluding soy). Five and a half percent of the patients used either hormone replacement therapy (HRT) or hormonal contraception at the pre-operative visit, after they had received their breast cancer diagnosis. In conclusion, it is important that doctors discuss the use of CAM and exogenous hormone therapy with their breast cancer patients given the prevalence of these drugs.
Abstract Background. Complementary and alternative medicine (CAM) use is common among breast cancer patients. Several CAM therapies may have negative side effects or interact with conventional therapies. We studied biologically based CAM use with and without vitamins/minerals in relation to patient and tumor characteristics as well as treatment in an ongoing prospective cohort of 855 primary breast cancer patients. Methods. Patients from two hospitals in southern Sweden were included. Pre-operative and follow-up questionnaires containing questions on food intake, lifestyle, and concomitant medications, including natural remedies, were completed up to five years postoperatively. Clinical information was obtained from clinical records and tumor characteristics from pathology reports. Results. CAM and/or vitamins/minerals were used by 34.2% pre-operatively and by 57.9% during at least one visit. Over 100 different preparations were reported. At least eight of the commonly used preparations may interact with conventional breast cancer therapies. CAM users more often had a BMI
CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy.
Pre- and postoperative questionnaires on lifestyle and concomitant medications were completed by 634 primary breast cancer patients between 2002 and 2008, among whom 333 patients had ER-positive tumors and received tamoxifen. CYP2D6*3, *4, *6, *10 and *41 were genotyped. Information on clinical data, breast cancer events, and tumor characteristics was obtained from patients' charts, population registries, the Regional Tumor Registry, and pathology reports.
Median follow-up was 4.9 years. Neither poor metabolizers (adjusted HR 0.50; 95% CI 0.07-3.82) nor intermediate metabolizers (adjusted HR 1.00; 95% CI 0.47-2.11) had an increased risk of early breast cancer events when compared with extensive metabolizers. CYP2D6 activity score (taking into account genotype and CYP2D6 inhibitor use) was not associated with early breast cancer events (LogRank, Ptrend = 0.44).
CYP2D6 genotype was not associated with tamoxifen treatment outcome, even when CYP2D6 inhibitor use, aromatase inhibitor use, or chemotherapy was taken into account. CYP2D6 genotype may be of minor importance for tamoxifen-treated patients in Scandinavia.
The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up, adj HR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (Pinteraction ?=?0.048), preoperative NSAID use (Pinteraction ?=?0.009), and tumor size (Pinteraction ?=?0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, adj HR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, adj HR 4.51 (1.18-11.44) as well as in patients with large tumors, adj HR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41 204 patients. The results were compared with those of a similar overview from 1996 including 285 982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas. There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate. There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival. There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy. There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy. There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy. There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival. There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients. There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate. There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival. There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies. There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics. There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the tumour bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up. There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences. There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy. There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn.