Dataset Information

The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands.

ABSTRACT: BACKGROUND: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. PATIENTS AND METHODS: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks. RESULTS: Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4-2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6-14.8) when <35 to 1.5 (95% CI 1.4-1.7) for > or =60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48-0.69) and chemotherapy (HR 0.73; 95% CI 0.60-0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33-1.56). CONCLUSION: Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection.

SUBMITTER: Schaapveld M

PROVIDER: S-EPMC2440941 | biostudies-other | 2008 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:ImportanceWithin 10 years after breast cancer diagnosis, roughly 5% of patients develop contralateral breast cancer (CBC). Randomized trials have found that therapy including tamoxifen citrate and aromatase inhibitors (AIs) reduces CBC risk. But little is known about the magnitude and duration of protective associations within the context of real-world clinical management settings, where varying durations of and gaps in treatment are common.ObjectiveTo determine the association between adjuvant tamoxifen and AI therapy and CBC risk within a general community setting.Design, setting, and participantsA retrospective cohort study of CBC risk among 7541 patients diagnosed with a first primary unilateral invasive breast cancer at Kaiser Permanente Institute for Health Research (Colorado) or Kaiser Permanente Northwest Center for Health Research (Oregon) between January 1, 1990, and December 31, 2008. Data were analyzed from 1 year after diagnosis of the first breast cancer through the earliest of the following events: CBC diagnosis, other second cancer diagnosis, death, last tumor registry follow-up, exit from the Kaiser Permanente health care plan, or end of study follow-up (December 31, 2010, for Oregon and December 31, 2011, for Colorado).ExposuresAdjuvant tamoxifen use and AI therapy were treated as time-dependent exposures, assessed using electronic prescription records.Main outcomes and measuresIncident CBC based on long-term systematic follow-up.ResultsAmong 7541 women with invasive breast cancer, median age at initial breast cancer diagnosis was 60.6 years (age range, 24.9-84.9 years). Women were predominantly (92.9% [7009 of 7541]) of white race. During a median of 6.3 years (range, 1-20.9 years) of follow-up, 248 women developed CBC (45 in situ and 203 invasive). Contralateral breast cancer risk decreased significantly with increasing tamoxifen therapy duration. In current users, the relative risk (RR) per year of tamoxifen use was 0.76 (95% CI, 0.64-0.89), with an estimated 66% (RR, 0.34; 95% CI, 0.29-0.40) RR reduction for 4 years of use compared with nonusers. Risk reductions were slightly smaller for past users but were still significant at least 5 years after stopping tamoxifen therapy (RR per year of use, 0.85; 95% CI, 0.71-0.995). In addition, AI use without tamoxifen therapy was associated with reduced CBC risk (RR for AI users compared with nonusers, 0.48; 95% CI, 0.22-0.97). Risk reductions were most apparent among women whose primary and CBCs were estrogen receptor positive.Conclusions and relevanceTamoxifen therapy was associated with reduced CBC risk during treatment and after its cessation, with risk progressively decreasing as tamoxifen therapy duration increased. Among those surviving at least 5 years, tamoxifen use for at least 4 years was estimated to prevent 3 CBCs per 100 women by 10 years after an estrogen receptor-positive first breast cancer, an absolute risk reduction that is consistent with findings from clinical trials. If adjuvant endocrine therapy is indicated for breast cancer treatment, these findings in concert with trial data suggest that women should be encouraged to complete the full course.

Project description:OBJECTIVE:High-deductible health plans (HDHPs) have become the predominant commercial health insurance arrangement in the US. HDHPs require substantial out-of-pocket (OOP) costs for most services but often exempt medications from high cost sharing. We examined effects of HDHPs on OOP costs and utilization of adjuvant hormonal therapy (AHT), which are fundamental care for patients with breast cancer. METHODS:This controlled quasi-experimental study used claims data (2003-2012) from a large national health insurer. We included 986 women with incident early-stage breast cancer, age 25-64 years, insured by employers that mandated a transition from low-deductible (??$500/year) to high-deductible (??$1000/year) coverage, and 3479 propensity score-matched controls whose employers offered only low-deductible plans. We examined AHT utilization and OOP costs per person-year before and after the HDHP switch. RESULTS:At baseline, the OOP costs for AHT were $40.41 and $36.55 per person-year among the HDHP and control groups. After the HDHP switch, the OOP costs for AHT were $91.76 and $72.98 per person-year among the HDHP and control groups, respectively. AHT OOP costs increased among HDHP members relative to controls but the change was not significant (relative change 13.72% [95% CI -?9.25, 36.70%]). AHT use among HDHP members did not change compared to controls (relative change of 2.73% [95% CI -?14.01, 19.48%]); the change in aromatase inhibitor use was -?11.94% (95% CI -?32.76, 8.88%) and the change in tamoxifen use was 20.65% (95% CI -?8.01, 49.32%). CONCLUSION:We did not detect significant changes in AHT use after the HDHP switch. Findings might be related to modest increases in overall AHT OOP costs, the availability of low-cost generic tamoxifen, and patient awareness that AHT can prolong life and health. Minimizing OOP cost increases for essential medications might represent a feasible approach for maintaining medication adherence among HDHP members with incident breast cancer.

Project description:AimThe estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an "in vivo"-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC.MethodsFrom a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients.ResultsCBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1.ConclusionsMetachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance "in vivo". The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. A different function for AIB1 in the tamoxifen treatment naïve vs. resistant setting is suggested, and may explain previously conflicting results where a high AIB1-expression has been correlated to both a good response to adjuvant tamoxifen and tamoxifen resistance.

Dataset Information

The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets