Treatment and survival disparities by ethnicity in New Zealand women with stage I–III breast cancer tumour subtypes

Purpose

This study aims to look at the distribution of different subtypes of stage I–III breast cancer in Māori and Pacific versus non-Māori/Pacific women, and to examine cancer outcomes by ethnicity within these different subtypes.

Method

This study included 9,015 women diagnosed with stage I–III breast cancer between June 2000 and May 2013, recorded in the combined Waikato and Auckland Breast Cancer Registers, who had complete data on ER, PR and HER2 status. Five ER/PR/HER2 subtypes were defined. Kaplan–Meier method and Cox proportional hazards model were used to examine ethnic disparities in breast cancer-specific survival.

Results

Of the 9,015 women, 891 were Māori, 548 were Pacific and 7,576 others. Both Māori and Pacific women were less likely to have triple negative breast cancer compared to others (8.6, 8.9 vs. 13.0%). Pacific women were more than twice as likely to have ER?, PR? and HER2+ cancer than Māori and others (14.2 vs. 6.0%, 6.7%). After adjustment for age, year of diagnosis, stage, grade and treatment, the hazard ratios of breast cancer-specific mortality for Māori and Pacific women with ER+, PR+ and HER2? were 1.52 (95% CI 1.06–2.18) and 1.55 (95% CI 1.04–2.31) compared to others, respectively. Māori women with HER2+ cancer were twice more likely to die of their cancer than others.

Conclusions

Outcomes for Māori and Pacific women could be improved by better treatment regimens especially for those with HER2+ breast cancer and for women with ER+, PR+ and HER2? breast cancer.

     

Black/white differences in treatment and survival among women with stage IIIB–IV breast cancer at diagnosis: a US population-based study

Introduction

Non-Hispanic black (NHB) women with breast cancer have poorer survival than non-Hispanic white (NHW) women. Although NHB women are more often diagnosed at later stages, it is less established whether racial disparities exist among women diagnosed with late-stage breast cancer, particularly when care is provided in the community setting.

Methods

Treatment and survival were examined by race/ethnicity among women diagnosed in 2012 with stage IIIB–IV breast cancer using the National Cancer Institute’s population-based Patterns of Care Study. Medical records were re-abstracted and treating physicians were contacted to verify therapy. Vital status was available through 2014.

Results

A total of 533 women with stage IIIB–C and 625 with stage IV tumors were included; NHW women comprised about 70% of each group. Among women with stage IIIB–C disease, racial/ethnicity variations in systemic treatment were not observed but there was a borderline association indicating worse all-cause mortality among NHB women (hazard ratio 1.52; 95% confidence interval (CI) 0.96–2.41). In contrast, among women with stage IV disease, borderline associations indicating NHB women were more likely to receive chemotherapy (OR 1.44, 95% CI 0.90–2.30) and, among those with hormone receptor-positive tumors, less likely to receive endocrine therapy (OR 0.60, 95% CI 0.35–1.04). All-cause mortality did not vary by race/ethnicity for stage IV disease (hazard ratio 0.92; 95% CI 0.68–1.25).

Conclusions

More research is needed to identify additional factors associated with the potential survival disparities among women with stage IIIB–C disease and potential treatment disparities among women with stage IV disease.

     

Metastatic relapse of stage I–III breast cancer in New Zealand

Purpose

This study aims to investigate the factors that influence the risk of metastatic relapse in women presenting with stage I-III breast cancer in New Zealand.

Methods

The study included women diagnosed with stage I–III breast cancer. Cumulative incidence of distant metastatic relapse was examined with the Kaplan–Meier method by cancer stage and subtype. Cox proportional hazards models were used to estimate the adjusted hazard ratio of developing recurrent metastatic breast cancer by cancer stage and biomarker subtype after adjustment for other factors.

Results

A total of 17,543 eligible women were identified. The 5-year cumulative incidence of metastatic recurrence was 3.7% for stage I, 13.3% for stage II and 30.9% for stage III disease. The adjusted hazard ratios (HR) of stage II and stage III breast cancer developing metastatic disease were 2.07 and 4.82 compared to stage I. The adjusted risk of distant metastatic relapse was highest for luminal B HER2- cancers (adjusted HR: 1.59 compared to luminal A disease). Higher grade cancers were associated with a higher risk of metastases. After adjustment, women aged 60–69 years and Asian women had the lowest risk of distant metastatic relapse.

Conclusions

The prognosis of women with locally invasive breast cancer differs greatly with the chance of developing metastatic disease depending on the stage of disease at diagnosis and the subtype. Grade of disease at diagnosis was also important. Māori or Pacific ethnicity did not influence the risk of developing metastatic disease, although Asian women seemed less likely to develop metastases.

     

A nested case–control study of adjuvant hormonal therapy persistence and compliance,and early breast cancer recurrence in women with stage I–III breast cancer

Background:

Non-persistence and non-compliance are common in women prescribed hormonal therapy for breast cancer, but little is known about their influence on recurrence.

Methods:

A nested case–control study of associations between hormonal therapy non-persistence and non-compliance and the risk of early recurrence in women with stage I–III breast cancer was undertaken. Cases, defined as women with a breast cancer recurrence within 4 years of hormonal therapy initiation, were matched to controls (1 : 5) by tumour stage and age. Conditional logistic regression was used to examine associations between early recurrence and hormonal therapy non-persistence and non-compliance.

Results:

Ninety-four women with breast cancer recurrence were matched to 458 controls. Women who were non-persistent (⩾180 days without hormonal therapy) had a significantly increased adjusted recurrence odds ratio (OR) of 2.88 (95%CI 1.11, 7.46) compared with persistent women. There was no significant association between low compliance (OR 1.30; 95% CI 0.74, 2.30) and breast cancer recurrence.

Conclusion:

Hormonal therapy non-persistence is associated with a significantly higher risk of early recurrence in women with stage I–III oestrogen receptor (ER)-positive breast cancer. This finding is consistent with results from randomized studies of hormonal therapy treatment duration and suggests that interventions to target modifiable risk factors for non-persistence are required.     

Fertility preservation with ovarian stimulation and time to treatment in women with stage II–III breast cancer receiving neoadjuvant therapy

Purpose

The aim of this study was to analyze the prevalence of mental disorders in breast cancer survivors using claims data from the Health Insurance Review and Assessment Service in South Korea. We also analyzed patterns of mental disorders with respect to the time of diagnosis and age.

Materials and methods

We confirmed mental disorders in a nationwide cohort of 87,843 people who were diagnosed with invasive breast cancer and underwent surgery between January 1, 2010 and December 31, 2014. We investigated the prevalence of mental disorders according to the time of diagnosis and age group. We also examined the utilization patterns of medical institutions and medical departments.

Result

From one year before a breast cancer diagnosis, 8430 patients were diagnosed with a mental disorder. Of those patients, 3256 were diagnosed with depression (38.6%) and 2739 with anxiety (32.5%). The overall frequency of mental disorders peaked within one month after the cancer diagnosis. The highest rate of increase after diagnosis was noted in stress reaction/adjustment disorders. Depression was relatively high in the young age group, and anxiety was high in the elderly group. In total, there were 59,111 claims for mental disorders. Over 70% (43,788) of claims for mental disorder treatment were from a psychiatry medical department.

Conclusion

Mental disorders in breast cancer survivors showed different patterns of prevalence according to time, age, and disease. Early intervention could be effective in controlling symptoms of mental disorder and could increase the quality of life for cancer survivors.

     

Can demographic,clinical and treatment-related factors available at hormonal therapy initiation predict non-persistence in women with stage I–III breast cancer?

Purpose

To investigate whether demographic, clinical and treatment-related risk factors known at treatment initiation can be used to reliably predict future hormonal therapy non-persistence in women with breast cancer, and to inform intervention development.

Methods

Women with stage I–III breast cancer diagnosed 2000–2012 and prescribed hormonal therapy were identified from the National Cancer Registry Ireland (NCRI) and linked to pharmacy claims data from Ireland’s Primary Care Reimbursement Services (PCRS). Non-persistence was defined as a treatment gap of ≥180 days within 5 years of initiation. Seventeen demographic, clinical and treatment-related risk factors, identified from a systematic review, were abstracted from the NCRI-PCRS dataset. Multivariate binomial models were used to estimate relative risks (RR) and risk differences (RD) for associations between risk factors and non-persistence. Calibration and discriminative performance of the models were assessed. The analysis was repeated for early non-persistence (<1 year of initiation).

Results

Within 5 years of treatment initiation 680 women (19.9%) were non-persistent. Women aged?<50 years (adjusted RR 1.41, 95% CI 1.16–1.70) and those prescribed antidepressants (RR 1.22, 95% CI 1.04–1.45) had increased risk of non-persistence. Married women (RR 0.82 95% CI 0.71–0.94) and those with prior medication use (RR 0.62 95% CI 0.51–0.75) had reduced risk of non-persistence. The area under the receiver-operating characteristic (ROC) curve for non-persistence was 0.61. Findings were similar for early non-persistence.

Conclusion

The risk prediction model did not discriminate well between women at higher and lower risk of non-persistence at treatment initiation. Future studies should consider other factors, such as psychological characteristics and experience of side-effects.

     

Are medical oncologists biased in their treatment of the large woman with breast cancer?

Purpose. Obesity and breast cancer are common conditions that often coexist. Concerns of relative overdosing of chemotherapy in the large cancer patient have led clinicians to apply empiric dose reductions, cap the body surface area (BSA) at 2m², or use ideal rather than actual body weight to calculate BSA. There are no data supporting or refuting these practices and their prevalence is unknown. We sought to determine the distribution of body size and prevalence of obesity in the breast cancer population of our cancer centre, and to determine clinician chemotherapy dosing practices in the era of modern adjuvant chemotherapy. Patients and methods. Women with invasive breast cancer receiving systemic therapy at our institution between 1980 and 1998 were identified and their recorded height and weight were used to calculate BSA and body mass index (BMI). We reviewed the first cycle adjuvant chemotherapy dosing practices from 1990–1998. The ideal dose of chemotherapy was calculated based on calculated BSA, and then contrasted with the actual dose received at cycle one. Discrepancies were recorded and categorized, using the largest single drug reduction if more than one drug was reduced. Results. Mean BMI in the systemic therapy population was 26.4±5.3kg/m², 54% were overweight, 2% severely obese and 18% moderately so. Their mean BSA was 1.7±0.2m² and only 5% had a BSA2m². In the adjuvant chemotherapy subgroup, most patients received >85% of their ideal dose. The mean dose reduction was 5.3±11.3% versus 9.9±11.3% in the BSA <2 and >2m² groups, respectively (p=0.02), and 4.3±8.2% versus 6.7±13.1% in the BMI <25 and 25kg/m² groups, respectively (p=0.008). While only 24% of chemotherapy dose reductions of 15% were in the BSA 2m² group, 76% were in the BMI 25kg/m² group. Conclusions. Obesity is prevalent in this breast cancer population. BSA is not a sensitive index of large body size. We consistently detected more frequent empiric dose reductions at cycle one of adjuvant chemotherapy, with reductions of greater magnitude in the largest women (BSA 2m²) and those who were overweight (BMI 25kg/m²).     

Erratum to: Fertility preservation with ovarian stimulation and time to treatment in women with stage II–III breast cancer receiving neoadjuvant therapy

Objective

Comorbidity among breast cancer survivors is prevalent, and adherence to medication management of comorbidities may be important for both chronic disease and cancer-related outcomes. Our objective was to determine characteristics associated with nonadherence to common chronic medications among breast cancer survivors.

Methods

We conducted a retrospective cohort study of 4216 women in an integrated care system diagnosed with early-stage breast cancer between 1990 and 2008 and alive without recurrence or second primary breast cancer in the second-year following diagnosis. Adherence to antihypertensives, oral diabetes medications, and statins was measured during the second-year post-breast cancer diagnosis using medication possession ratios (MPR). Nonadherence was defined as MPR <0.80. We estimated odds ratios (OR) and 95% confidence intervals (CI) for nonadherence to antihypertensives, oral diabetes medications, and statins by various characteristics using multivariable logistic regression.

Results

Among 2308 users of antihypertensives (n = 1779), diabetes medications (n = 499) and/or statins (n = 1072), 37% were nonadherent to antihypertensives; 75% were nonadherent to diabetes medications; 39% were nonadherent to statins. In adjusted models, younger age was associated with nonadherence to all three therapeutic classes. Certain cancer treatments were associated with nonadherence to antihypertensives (radiation: OR 1.21, 95% CI 1.01–1.47; endocrine therapy: OR 1.27, 95% CI 1.03–1.52) and diabetes medications (chemotherapy: OR 1.69, 95% CI 1.17–2.21). Less frequent primary care provider visits were associated with higher odds of nonadherence to antihypertensives (OR 1.70, 95% CI 1.19–2.22); and trends showed higher Charlson comorbidity scores associated with greater adherence to diabetes medications (P < 0.001) and statins (P = 0.032).

Conclusions

Nonadherence to medications is high among breast cancer survivors, particularly diabetes medications, and is associated with cancer treatments and other patient characteristics. Additional research is warranted to understand the needs of cancer patients taking chronic medications and explore patient and provider factors influencing adherence.

     

Racial and ethnic disparities in the diagnosis of breast cancer: changes in presenting stage in minority populations in Florida during 1981–2009

We assessed whether presenting breast cancer stage has changed over time in Florida, and whether there is variation in this change with respect to race, ethnicity, and socioeconomic status (SES). Data were obtained from the Florida Cancer Data System. We included females with invasive breast cancer and complete information on race, ethnicity, and SES during 1981–2009 (n = 226,651). Associations between categorical variables were examined using Chi-square tests. Predictors of SEER stage at diagnosis (local, regional, and distant) were modeled with multinomial ordinal logistic regression models. There was a significant increase in local disease and a decrease in regional and distant disease at presentation (p < 0.0001) over the time period assessed. Compared to whites, black patients continue to have lower odds of local presentation (OR 0.73, 95 % CI 0.63, 0.85), as do Hispanic patients (OR 0.80, 95 % CI 0.76, 0.84) compared to non-Hispanics. The increase in local stage at diagnosis was greater for black than white patients, as was the decrease in regional and distant disease (p < 0.001). Hispanic women also had significant increase in localized disease and decrease in regional and distant disease (p < 0.001), but there was little difference in the change compared to non-Hispanic women. Localized breast cancer stage at diagnosis has become more common over time in all groups. Significant disparity persists, with black and Hispanic patients being less likely to present with localized disease than white patients overall. There was a greater change for black versus white patients, resulting in a narrowing in the racial gap in stage at diagnosis.     

Do radiation use disparities influence survival in patients with advanced breast cancer?

BACKGROUND:

The authors previously identified racial/ethnic disparities in the use of radiation therapy (RT) in patients with advanced breast cancer (BC). They hypothesized that disparities in the use of RT were associated with survival differences favoring white patients.

METHODS:

The authors used the Surveillance, Epidemiology, and End Results database to identify white, black, Hispanic, and Asian patients with BC associated with ≥10 metastatic lymph nodes diagnosed between 1988 and 2005. Multivariate analyses of overall survival (OS) and disease‐specific survival (DSS) assessed age, sex, race, tumor size, histology, estrogen receptor status, progesterone receptor status, RT, and type of surgery. The authors further stratified for use of RT and type of surgery. Risk of mortality was reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS:

Of 15,895 patients with advanced BC, 12,653 met entry criteria. On multivariate analysis, RT was associated with a decreased risk of all‐cause (HR, 0.78; 95% CI 0.74‐0.83; P < .001) and disease‐specific (HR, 0.81; 95% CI, 0.76‐0.86; P < .001) mortality; black race was associated with an increased risk of all‐cause (HR, 1.54; 95% CI, 1.42‐1.68; P < .001) and disease‐specific (HR, 1.53; 95% CI, 1.39‐1.68; P < .001) mortality. After stratifying by type of surgery and use of RT, blacks demonstrated poorer survival than their white counterparts, regardless of surgery type or receipt of RT.

CONCLUSIONS:

Only black patients had poorer OS and DSS relative to whites. When stratified by type of surgery and use of RT, blacks continued to demonstrate poorer survival. This survival disparity is unlikely to be because of lack of RT. Cancer 2012;. © 2011 American Cancer Society.     

PIK3CA-activating mutations and chemotherapy sensitivity in stage II–III breast cancer

Introduction

In vitro evidence suggests that PIK3CA (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide) activation may be associated with altered chemotherapy sensitivity in cancer.

Methods

Tumor DNA from 140 patients with stage II–III breast cancer undergoing neoadjuvant chemotherapy was sequenced for PIK3CA mutations on exons 1, 9, and 20. Mutation status was correlated with clinical/pathological parameters and chemotherapy response as (a) pathological complete response (pCR) versus residual cancer or (b) quantitative residual cancer burden (RCB) scores, including stratification for estrogen receptor (ER) expression status, type of chemotherapy, and by exons.

Results

Twenty-three patients (16.4%) harbored a PIK3CA mutation, with 12, 11, and 0 mutations located in exons 9, 20, and 1, respectively. PIK3CA exon 9 mutations were more frequent among node-negative (52% versus 25%; P = 0.012) than node-positive tumors, particularly among ER-positive tumors. pCR rates and RCB scores were similar among patients with the wild-type and mutant PIK3CA genes, even after stratification by ER status, chemotherapy regimen (anthracycline versus anthracycline plus paclitaxel), or exon.

Conclusion

PIK3CA mutations are not associated with altered sensitivity to preoperative anthracycline-based or taxane-based chemotherapies in ER-positive and ER-negative breast tumors. In this study, PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors.     

Expression of β-tubulin III and survivin in advance stage breast cancer correlates with chemotherapeutic effects of docetaxel

Aims: To investigate the relationship between the expression of β-tubulinⅢ and survivin in advanced breastcancers and chemotherapeutic effects of docetaxel. Methods: Clinical pathological data of 74 patients withadvanced breast cancer were retrospectively analyzed after docetaxel chemotherapy. Expression of β-tubulinⅢand survivin was assessed by immunohistochemistry and analyzed with reference to therapeutical and adverseeffects of docetaxel. Results: The positive expression rate of β-tubulinⅢ was 38.1% (32/84), while that of survivinwas 76.2% (64/84). The effective rate (complete response + partial response) was 52.4%. That for patients withthe positive expression of β-tubulinⅢ or/and survivin was significantly lower than for those with negativeexpression (P<0.05). There were significant differences in the non-progression of median diseases, 1-year and2-year survival rates of between the patients with positive and negative expression (P<0.05). The main side effectswere myelosuppression, alimentary canal response and alopecie, no differences being observed between groups.Conclusions: The combined detection of β-tubulinⅢ and survivin is a predictive index for chemotherapy effectsof docetaxel in metastatic breast cancer.     

Does stage at diagnosis explain the difference in survival after breast cancer in Denmark and Sweden?

Breast cancer survival differs 9 percentage points between the neighbouring countries of Denmark and Sweden. The authors' aim was to analyse whether this was caused by early detection in Sweden. The extent of disease and outcome was compared in two population-based breast cancer cohorts in 1983-1989. Breast cancer management was decentralized in Denmark without mammography screening whereas treatment in Sweden was centralized and the population partly screened. Ten- and 15-year relative survival was 15% and 6% higher in Sweden (p<0.001) with corresponding differences in crude and disease-specific survival. Stage distribution was significantly more favourable in the Swedish cohort. In multivariate analysis age, tumour size, extent of axillary surgery, and spread affected survival; however, the impact of region persisted (p<0.001). Reanalysis without screening-detected patients only slightly affected the impact of region. It was concluded that early detection had significant impact on survival but other regional differences might be of importance.     

Racial/ethnic and socioeconomic disparities in mortality among women diagnosed with cervical cancer in New York City, 1995–2006

Background  

Though cervical cancer rates have declined due to Pap screening, racial and socioeconomic disparities in cervical cancer incidence and mortality persist. This study assesses the relative impact of race/ethnicity and neighborhood poverty on cervical cancer incidence and mortality in New York City (NYC).     

Comparison of clinicopathologic features and survival in young American women aged 18–39 years in different ethnic groups with breast cancer

Background:

Ethnic disparities in breast cancer diagnoses and disease-specific survival (DSS) rates in the United States are well known. However, few studies have assessed differences specifically between Asians American(s) and other ethnic groups, particularly among Asian American(s) subgroups, in women aged 18–39 years.

Methods:

The Surveillance, Epidemiology, and End Results database was used to identify women aged 18–39 years diagnosed with breast cancer from 1973 to 2009. Incidence rates, clinicopathologic features, and survival among broad ethnic groups and among Asian subgroups.

Results:

A total of 55 153 breast cancer women aged 18–39 years were identified: 63.6% non-Hispanic white (NHW), 14.9% black, 12.8% Hispanic-white (HW), and 8.7% Asian. The overall incidence rates were stable from 1992 to 2009. Asian patients had the least advanced disease at presentation and the lowest risk of death compared with the other groups. All the Asian subgroups except the Hawaiian/Pacific Islander subgroup had better DSS than NHW, black, and HW patients. Advanced tumour stage was associated with poorer DSS in all the ethnic groups. High tumour grade was associated with poorer DSS in the NHW, black, HW, and Chinese groups. Younger age at diagnosis was associated with poorer DSS in the NHW and black groups.

Conclusion:

The presenting clinical and pathologic features of breast cancer differ by ethnicity in the United States, and these differences impact survival in women younger than 40 years.     

Mindfulness significantly reduces self-reported levels of anxiety and depression: Results of a randomised controlled trial among 336 Danish women treated for stage I–III breast cancer

IntroductionAs the incidence of and survival from breast cancer continue to raise, interventions to reduce anxiety and depression before, during and after treatment are needed. Previous studies have reported positive effects of a structured 8-week group mindfulness-based stress reduction program (MBSR) among patients with cancer and other conditions.PurposeTo test the effect of such a programme on anxiety and depression among women with breast cancer in a population-based randomised controlled study.MethodsA total of 336 women who had been operated on for breast cancer (stage I–III) were randomised to usual care or MBSR + usual care. Questionnaires including the Symptom Checklist-90r anxiety and depression subscales and the Center for Epidemiological Studies-Depression scale were administered before randomisation and immediately, 6 and 12 months after the intervention.ResultsIntention-to-treat analyses showed differences between groups in levels of anxiety (p = 0.0002) and depression (SCL-90r, p < 0.0001; CES-D, p = 0.0367) after 12 months. Graphical comparisons of participants with higher levels of anxiety and depression at baseline showed a significantly greater decrease in the intervention group throughout follow-up and no differences among least affected participants. Medium-to-large effects were found for all outcomes in the intervention group in analyses of change scores after 12 months’ follow-up.ConclusionThe 8-week group based MBSR intervention had clinically meaningful, statistically significant effects on depression and anxiety after 12 months’ follow-up, and medium-to-large effect sizes. Our findings support the dissemination of MBSR among women with breast cancer. (Clintrials.gov No.: NCT00990977).     

Detection of extra-axillary lymph node involvement with FDG PET/CT in patients with stage II–III breast cancer

PurposeThe aim of this prospective study was to assess the incidence of extra-axillary lymph node involvement on baseline FDG PET/CT in patients with stage II–III breast cancer scheduled for neo-adjuvant chemotherapy.MethodsPatients with invasive breast cancer of >3 cm and/or proven axillary lymph node metastasis were included for before neo-adjuvant chemotherapy. Baseline ultrasound of the infra- and supraclavicular regions was performed with fine-needle biopsy as needed. Subsequently FDG PET/CT was performed. All visually FDG-positive nodes were regarded as metastatic based on the previously reported high specificity of the technique.ResultsSixty patients were included. In 17 patients (28%) extra-axillary lymph nodes were detected by FDG PET/CT, localised in an intra-mammary node (1 lymph node in 1 patient), mediastinal (2 lymph nodes in 2 patients), internal mammary chain (9 lymph nodes in 8 patients), intra- and interpectoral (6 lymph nodes in 4 patients), infraclavicular (5 lymph nodes in 4 patients) and in the contralateral axilla (3 lymph nodes in 2 patients). Ultrasound-guided cytology had detected extra-axillary lymph node involvement in seven of these patients, but was unable to detect extra-axillary nodes in the other 10 patients with positive extra-axillary lymph nodes on FDG PET/CT. Radiotherapy treatment was altered in 7 patients with extra-axillary involvement (12% of the total group).ConclusionsFDG PET/CT detected extra-axillary lymph node involvement in almost one-third of the patients with stage II–III breast cancer, including regions not evaluable with ultrasound. FDG PET/CT may be useful as an additional imaging tool to assess extra-axillary lymph node metastasis, with an impact on the adjuvant radiotherapy management.     

Predictors of timing of adjuvant chemotherapy in older women with hormone receptor–negative,stages II–III breast cancer

Adherence to consensus guidelines for cancer care may vary widely across health care settings and contribute to differences in cancer outcomes. For some women with breast cancer, omission of adjuvant chemotherapy or delays in its initiation may contribute to differences in cancer recurrence and mortality. We studied adjuvant chemotherapy use among women with stage II or stage III, hormone receptor–negative breast cancer to understand health system and socio-demographic correlates of underuse and delayed adjuvant chemotherapy. We used Surveillance Epidemiology and End Results (SEER)-Medicare linked data to examine the patterns of care for 6,678 women aged 65 and older diagnosed with stage II or stage III hormone receptor–negative breast cancer in 1994–2002, with claims data through 2007. Age-stratified logistic regression was employed to examine the potential role of socio-demographic and structural/organizational health services characteristics in explaining differences in adjuvant chemotherapy initiation. Overall utilization of guideline-recommended adjuvant chemotherapy peaked at 43% in this population. Increasing age, higher co-morbidity burden, and low-income status were associated with lower odds of chemotherapy initiation within 4 months, whereas having positive lymph nodes, more advanced disease, and being married were associated with higher odds (P < 0.05). Health system–related structural/organizational characteristics and race/ethnicity offered little explanatory insight. Timely initiation of guideline-recommended adjuvant chemotherapy was low, with significant variation by age, income, and co-morbidity status. Based on these findings, future studies should seek to explore the more nuanced reasons why older women do not receive chemotherapy and why delays in care occur.     

Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004–2010

Nearly a decade ago, researchers identified a potential interaction between tamoxifen and strong CYP2D6 inhibitors, including several frequently used antidepressants. Based on evidence available at that time, a United States Food and Drug Administration advisory committee recommended tamoxifen’s label be changed in October 2006, noting that postmenopausal women with estrogen receptor-positive breast cancer who are poor CYP2D6 metabolizers by genotype or drug interactions may be at increased risk of cancer recurrence. The impact of accumulating drug risk information on antidepressant use is unknown. We conducted a retrospective, longitudinal cohort study of 13,205 women aged 50–95 with breast cancer initiating tamoxifen between July 2004 and December 2009. We evaluated trends in strong, moderate, and weak CYP2D6-inhibitor antidepressants and tamoxifen co-prescribing and factors associated with ongoing strong inhibitor use. A propensity score matched control group (aromatase inhibitor initiators) was used to estimate changes in co-prescribing, accounting for secular trends. In each month, approximately 24 % of tamoxifen and aromatase inhibitor users were prescribed antidepressants. Among women using tamoxifen and antidepressants, 34 % used strong inhibitors between 2004 and 2006 versus 15 % in 2010. Strong inhibitor use decreased more among tamoxifen users than aromatase inhibitor users (difference-in-differences [DD] ?0.09; 95 % confidence interval [CI] ?0.15, ?0.03). Weak inhibitor use increased among tamoxifen users from 32 % between 2004 and 2006 to 52 % in 2010, more rapidly than among aromatase inhibitor users (DD 0.15; CI 0.08, 0.23). The factor most strongly associated with strong inhibitor and tamoxifen co-prescribing after 2006 was prior strong inhibitor use (RR 4.73; CI 3.62–6.18). In conclusion, there were substantial declines in strong CYP2D6-inhibitor use among tamoxifen users following dissemination of information suggesting a potential for increased risk with co-prescribing. Whether patients and providers will continue to avoid strong inhibitor antidepressants is yet to be seen, but clinicians appear to be responsive to drug interaction risk information in this setting.     

Phase I trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor–positive metastatic breast cancer

Purpose

Obese women with breast cancer have worse prognosis than women with normal body mass index. Endocrine therapy resistance is in part mediated by insulin resistance in obese women with breast cancer. We investigated the tolerability and pharmacokinetics of exemestane in combination with metformin and rosiglitazone in nondiabetic overweight and obese postmenopausal women with hormone receptor–positive metastatic breast cancer.

Methods

Patients had previously received chemotherapy and endocrine therapy for breast cancer. Exemestane was given as 25 mg orally per day. Metformin (M) and rosiglitazone (R) were given twice daily. Dose level 1 consisted of M 1,500 mg/day and R 6 mg/day. Dose level 2 consisted of M 2,000 mg/day and R 8 mg/day. Plasma concentrations of exemestane were measured on days 1, 8, and 15.

Results

Twenty patients were enrolled. Fourteen patients received exemestane, metformin, and rosiglitazone. Six patients received exemestane with metformin only (2,000 mg/day). Both regimens were well tolerated at the highest doses tested, and there were no notable changes in plasma exemestane levels. Six patients (30 %) had stable disease for 6 months or longer.

Conclusions

Oral daily administration of exemestane (25 mg) and metformin (2,000 mg) with and without rosiglitazone (8 mg) daily was well tolerated. Exemestane pharmacokinetics were not altered by metformin and rosiglitazone.