Positive Early Stage Breast Cancer Research Articles

Late Extended Adjuvant Treatment With Letrozole Improves Outcome in Women With Early-Stage Breast Cancer Who Complete 5 Years of Tamoxifen

The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P = .02). Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.

Managing Bone Loss in Women with Early-Stage Breast Cancer Receiving Aromatase Inhibitors

Third-generation aromatase inhibitors (AIs; anastrozole, letrozole, exemestane) have replaced tamoxifen as the adjuvant treatment of choice for postmenopausal women with hormone receptor–positive early-stage breast cancer. Because bone loss is a predictable adverse event of AI therapy, early recognition, prevention, and/or treatment of AI-induced bone loss is needed. One to 5 years of AI therapy causes a bone mineral density (BMD) loss of up to 7.2% in postmenopausal women; however, current clinical guidelines do not recommend initiating bisphosphonate therapy for the treatment of BMD loss until fragility fractures or frank osteoporosis occur. Results of recent trials evaluating the use of intravenous (I.V.) zoledronic acid as prevention and treatment of AI-induced bone loss in women with early-stage breast cancer receiving letrozole suggest a potential benefit to the concurrent use of zoledronic acid and letrozole. To our knowledge, clinical trials assessing oral or other I.V. bisphosphonates for these indications have not been published. Recently, concerns of bisphosphonate-induced renal safety and osteonecrosis of the jaw have emerged. Studies evaluating bisphosphonates in women with breast cancer have reported lower rates of renal dysfunction than those reported in patients with metastatic cancer receiving bisphosphonates, and no cases of jaw osteonecrosis. The use of bisphosphonates in this population requires further study to more clearly define the most appropriate timing and length of therapy as well as the long-term efficacy and safety of these drugs. Until these data become available, balancing the safety concerns with the potential benefits of I.V. bisphosphonates to minimize or prevent AI-induced bone loss in women with early-stage breast cancer is required.

The Prognostic Biomarkers HOXB13, IL17BR, and CHDH Are Regulated by Estrogen in Breast Cancer

We previously identified three genes, HOXB13, IL17BR, and CHDH, that strongly predict clinical outcome in estrogen receptor (ER)-positive breast cancer patients receiving tamoxifen monotherapy. The biological mechanisms linking these genes to estrogen signaling and tamoxifen response in breast cancer remain to be determined. In a consecutive series of 148 ER-positive and ER-negative breast cancers, HOXB13, IL17BR, and CHDH gene expression was measured by quantitative real-time PCR and correlated with ER, PR, and HER2 expression. The role of estrogen and ER in the regulation of these three genes was assessed in several ER-positive and ER-negative breast cancer cell lines. In primary breast tumors, HOXB13 expression correlated negatively, and IL17BR and CHDH expression correlated positively, with ER status, and all three genes exhibited an ER-dependent correlation pattern with HER2 status that differs from PR and PS2, two canonical estrogen-regulated genes. Results using breast cancer cell lines show that these genes are regulated by estradiol in an ER-dependent manner, and that this regulation is abrogated by tamoxifen. HOXB13, IL17BR, and CHDH are estrogen-regulated genes, but their pattern of correlation with known positive (ER, PR) and negative (HER2) predictors of tamoxifen response differs from canonical ER signature genes. These results provide a biological rationale for the prognostic utility of these three genes in early-stage ER-positive breast cancer and for their potential to predict anti-estrogen resistance.

Partial Breast Irradiation Versus Whole Breast Radiotherapy for Early-Stage Breast Cancer: A Decision Analysis

To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adjusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.

Human Epidermal Growth Factor Receptor 2 Status Correlates With Lymph Node Involvement in Patients With Estrogen Receptor (ER) –Negative, but With Grade in Those With ER-Positive Early-Stage Breast Cancer Suitable for Cytotoxic Chemotherapy

Human epidermal growth factor receptor 2 (HER-2) expression is associated with increased risk of high-grade disease, nodal metastasis, and absence of estrogen receptors (ERs) in early breast cancer. We tested interactions between ER and HER-2 to determine if they may modulate breast cancer nodal metastasis and proliferation. Tumors from the Cancer Research UK Taxotere as Adjuvant Chemotherapy phase III trial were tested for HER-2 using current diagnostic procedures. ER status, progesterone status, clinicopathologic characteristics, and patient age were included in a logistic regression analysis to identify associations with HER-2 status (positive v negative). A total of 841 (23.6%) of 3,565 samples were HER-2 positive (3+ by immunohistochemistry or positive by fluorescent in situ hybridization). ER-negative tumors were more likely to be HER-2 positive than were ER-positive tumors (odds ratio [OR] = 1.87, ER negative v ER positive; P < .001). For ER-positive tumors, risk of HER-2 positivity increased by grade (OR = 7.6, grade 3 v grade 1; P < .001) but not nodal status (OR = 1.3, four or more positive nodes v node negative; P = .08). Conversely, ER negative node-positive tumors were markedly more frequently HER-2 positive than node-negative cases (OR = 3.05, four or more positive nodes v node negative; P < .001) but independent of grade (OR = 0.82, grade 3 v grade 1; P = .76). In early breast cancer patients selected for cytotoxic chemotherapy, we identified significant interactions between HER-2 and ER expression that correlate with tumor pathology. In ER-positive breast cancers, HER-2 expression correlates with grade, not nodal metastasis. In ER-negative breast cancers, HER-2 expression correlates with increased nodal positivity, not grade. ER and HER-2 expression may modify tumor pathology via ER/HER-2-mediated cross talk.

Partial-Breast Irradiation Versus Whole-Breast Irradiation for Early-Stage Breast Cancer: A Decision Analysis

Purpose—To compare the quality-adjusted life expectancy (QALE) between women treated with whole-breast radiation therapy (WBRT) and partial-breast irradiation (PBI) for estrogen-receptor (ER)-positive early-stage breast cancer. Methods and materials—We developed a Markov model to describe health states in the 15 years following radiotherapy (RT) for ER-positive early-stage breast cancer. Breast recurrences were separated into local recurrences (LR) and elsewhere failures (EF). Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 years and aged 55 years), both of whom received adjuvant tamoxifen. Results—Assuming a NED-PBI (no evidence of disease) utility of 0.93, QALE after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio (HR) for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall, the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. Conclusions—For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent upon patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.

Adjuvant Therapy for ER-Positive Breast Cancer: Shaping the Role of Aromatase Inhibitors

The benefits of incorporating an aromatase inhibitor (AI) into adjuvant therapy for estrogen-receptor (ER)–positive early-stage breast cancer are no

Phase I/II study of a 3 weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive (HER2+) early stage breast cancer (ESBC) patients (pt). GEICAM 2003–03 study

11032 Background: The liposome-encapsulated form of doxorubicin (Myocet™) (M) seems to be safe in terms of cardiotoxicity in combination with standard doses of trastuzumab (H) and paclitaxel in BC. This phase I/II study of M, H, docetaxel (T) and pegfligrastrim (N) was designed to evaluate the efficacy and safety of the combination, and define the MTD, in order to examine the selected regimen in a phase II trial. Methods: Cohorts of 3 HER2+ (FISH+) ESBC pt were treated at fixed dose of N (6 mg) and H (2 mg/kg/week). M and T were administered at the following dose levels (DL) (mg/m2): DL0, 60/75; DL-1, 55/75; DL-2, 50/70; DL-3, 50/65; DL-4, 50/60. The MTD was defined as &gt;1/6 pt in any cohort experiencing a predefined dose-limiting toxicity (DLT) in cycle (cy) 1 or 2. LVEF was assessed at baseline and every 2 cy. Results: Nineteen pt have been enrolled in phase I; all are evaluable for efficacy and toxicity. Median age was 45. Twelve pt (63%) were premenopausal. Median tumour size was 45 mm (20–80); 13 (68%) and 6 pt (32%) presented with stage II and IIIA BC respectively. Six (32%) of tumours were G3. DLT were G3 diarrhoea, febrile neutropenia, thrombocytopenia, infection, and G4 asthenia. Three additional pt were treated at DL-4 for confirmation of the recommended dose; none of them had a DLT. One pt (DL-2) experienced asymptomatic, reversible LVEF decrease to 49%. All pt have been assessed for pathological response: 6 (32%) and 5 pt (26%) achieved one pCR and one pPR in breast, defined as Miller and Payne score of 5 and 4, respectively. Conclusions: Concomitant administration of M plus THN is highly active regimen with manageable toxicity in pt with HER2+ ESBC tumours. DL-4 has been selected as the DL for the ongoing phase II study with an enrolment target of 59 pt. No significant financial relationships to disclose.

International comparison of the cost-effectiveness of 5 years letrozole or anastrozole compared to 5 years tamoxifen for early breast cancer in hormone receptor-positive postmenopausal women: Belgium, Canada, UK, and US analyses

556 Background: The BIG1–98 and ATAC trials have proven the effectiveness of 5 years letrozole (LET) and anastrozole (ANA), respectively, compared to 5 years tamoxifen (TAM) for the treatment of postmenopausal women with hormone receptor positive (HR+) early stage breast cancer. This analysis uses similar assumptions to those used in the NICE appraisal in the UK, and country specific input data to estimate the cost-effectiveness of LET vs TAM and ANA vs. TAM from the Belgian, Canadian, UK, and US health care perspective (8 analyses). Methods: The same Markov model was used to estimate the incremental cost per quality-adjusted life year (QALY) gained (ICQ) across the 8 analyses in postmenopausal women with HR+ early stage breast cancer. Model events and assumptions were based on the analysis undertaken by the NICE appraisal team in the UK. Probabilities of breast cancer events (contralateral; locoregional; and metastases) were based on the latest early breast cancer (Lancet) overview. Country-specific cost, utility, and adverse event parameter values were informed by relevant population-based studies. LET and ANA effects were informed by published results of the BIG 1–98 and ATAC trials, which were assumed to cease after therapy discontinuation (other than fracture risk that continued for 5 further years). Costs and QALYs were estimated over the remaining lifetime of a cohort of HR+ women aged 60 yrs, discounted at 3.5% annually. Conclusion: Compared to TAM, adjuvant treatment of postmenopausal HR+ women with LET or ANA for 5 years is a cost-effective use of resources in all of the countries included in this analysis. Based on the model assumptions used by the NICE appraisal team in the UK, the mean results indicate that LET is more cost-effective than ANA, though the confidence intervals are wide. [Table: see text] No significant financial relationships to disclose.

Who Will Do the Work? What Work Will They Do?

in the United States. 2 This first-pass determination was done during a time when the expense of oncology care was starting to become an issue, in an era of more rudimentary cancer treatments, and on a background of proposals to reduce oncologytraining slots by 40%. The then-estimated 3,600 full-time-equivalent oncologists were adequate, based on comparisons with staff model health maintenance organizations’ (HMOs) use of oncologists per 100,000 population. Though this estimate of the workforce size was almost certainly wrong, the earlier study’s two main conclusions are largely true: oncologists desired delivering less primary care, and the workforce was right-sized. Fifteen years on, most oncologists are as busy as they want to be, and they spend their professional time delivering specialty oncology care. The current study used many data sources (both existing and new data from four surveys) to provide a more reliable estimate of the current oncology workforce—the American Medical Association Masterfile of physicians—and a more robust estimate of the potential patient population and oncology practice patterns. The results indicate that we will be facing a shortage of 2,550 to 4,080 oncologists by 2020 —which could translate to 9.4 to 15 million fewer oncologist visits. The study used a combination of Medicare visit data and National Cancer Institute incidence and prevalence projections to determine the demand for services and capacity of the workforce to deliver those services. The authors performed sensitivity analyses, testing the effects of increasing oncology training slots, electronic medical record use, and midlevel provider use on visit capacity and workforce supply. Projections were also made on the effects of delaying retirement of current oncologists and potential for decreased work hours and thus productivity in younger oncologists. The model’s sensitivity to increases in the number of new cancer patients seen by an oncologist, to varying the intensity of oncologist interaction with each patient, and to truncation of oncologist interaction with each patient by use of hospice or primary care providers to manage various stages of the illness was tested. Making predictions, especially about the future, is difficult, as was observed by both the theoretical physicist Niels Bohr and the applied physicist Yogi Berra. The wildest swings in the predictive model for visit demand (Table 4) occur when the proportion of new cancer cases seen by an oncologist is varied. 1 Many other specialists manage early-stage colon, skin, and prostate cancers. Medical oncologists add little value to management of these early-stage tumors, but radical changes in the management of these conditions (effective adjuvant systemic therapy for early-stage, high-risk prostate and colon cancers for instance) could radically alter the demand forecast. On the contrary, simplification in the management of hormone receptor–positive early-stage breast cancer could lead to more management of this now-common condition by surgeons or other nononcologists. It is difficult to predict the changes in practice patterns that biomedical or information technology will bring 15 years from now. Market forces should be allowed to continue to guide adjustments of oncology care. The reason medical oncologists see less early-stage prostate and skin cancer is that we currently add little value to the care of these patients. As oncologists become relatively rarer and our time more dear, we will figure out ways to become more productive diagnosticians, innovators, and problem solvers. We will spend less professional time performing extensive documentation and other non–value-added tasks, and more time developing and leading our teams. We should develop and refine guideline-based care so that we can delegate more routine tasks to midlevel providers, experienced oncology nurses, and others who specialize in managing various aspects of the cancer care continuum. Information technology should be developed to allow us to spend more productive time with our patients. Those new associates who are identified and hired should add value to patient care and only do work for which a trained medical oncologist is required.

Cost Effectiveness of Trastuzumab in the Adjuvant Treatment of Early Breast Cancer

Recent randomised trials have demonstrated a statistically significant effect of trastuzumab on disease-free survival when used as adjuvant therapy for human epidermal growth factor receptor 2 protein (HER2)-positive resectable early stage breast cancer, with a treatment course lasting either 9 or 52 weeks. However, the cost effectiveness of adjuvant trastuzumab with respect to mortality remains uncertain, especially in an Australian setting. To estimate the cost effectiveness of trastuzumab in Australia, in a cohort of 50-year-old patients with HER2-positive breast cancer over a lifetime, using (i) disease-free survival and cardiotoxicity data from recent randomised trials; (ii) information on long-term survival of patients with treated primary breast cancer; and (iii) costs of treating local and distant relapses and disease from causes other than breast cancer. A Markov model consisting of four health states (remission, loco-regional recurrence, metastatic disease and death) was developed. Transition probabilities corresponded to patterns of relapse and metastases seen in recent trials. The model was run until age 100 years to allow calculation of average survival. Outcome measures were life-years and QALYs (calculated using utility weights reported in the literature). The model was calibrated to reflect literature evidence that the risk of breast cancer recurrence following primary treatment diminishes progressively to zero after about 20 years. It was assumed that the morbidity benefit of trastuzumab observed in trials would be present for 5 years but would then diminish progressively to zero after 8 years. Costs (year 2005 values) and benefits were discounted at 3% per annum. For every 1000 patients treated with a 52-week course of trastuzumab, there were 136 fewer breast cancer deaths (relative risk reduction 28%). The incremental cost-effectiveness ratios (ICERs) were Australian dollars ($ A)13 730 per year of life saved (YOLS) and $ A22 793 per QALY. The net incremental cost was $ A56.3 million ($ A414 012/cancer death avoided). Cost effectiveness declined (ICER = $ A27 734/QALY) in older patients (age 65 years at treatment initiation). The ICER was driven mainly by the drug acquisition costs, the assumption of the duration of benefit and the discount rate. Cost offsets from reduced costs of treating recurrent or metastatic breast cancer during follow-up were present but these factors were of less importance according to sensitivity analyses. The 9-week treatment schedule approached economic dominance (ICER = $ A1700/QALY) because of decreased costs, improved relative risk for prevention of metastases and more cancer deaths avoided (196). The results suggest that trastuzumab as adjuvant therapy for early breast cancer may be cost effective when given over either 52 or 9 weeks at current acquisition costs in Australia. However, the overall budget impact of the 52-week course is significant, and the 9-week course appears economically attractive.

Aromatase-Inhibitor–Induced Joint Complaints: An Underappreciated Problem?

Adjuvant aromatase inhibitors (AIs) are now the standard of care for postmenopausal women with hormone-receptor–positive early-stage breast cancer. Which is the optimal AI and how it should be used remain open questions; however, in the large clinical trials in which adjuvant AIs (either in lieu of tamoxifen or sequentially after tamoxifen) have been investigated, researchers have noted improvements in patient outcomes, largely in disease-free survival (DFS). In all the trials that have included AIs, musculoskeletal (MS) and joint complaints were more common in patients who received an AI than in those who received tamoxifen alone. For example, in the ATAC trial (Journal Watch Women’s Health Sep 24 2002), in which 5 years of tamoxifen was compared with 5 years of …

A population-based study of trastuzumab-mediated cardiotoxicity among early stage breast cancer patients treated with adjuvant trastuzumab

10640 Background: Given the risk of cardiotoxicity demonstrated with trastuzumab (T) in the MBC literature, adjuvant T trials incorporated stringent cardiac monitoring. In 2005, several of these trials were reported with impressive DFS improvements. As a result of these trials, women in the province of British Columbia with HER-2 positive early stage breast cancer were offered T either concurrently or sequentially with their primary chemotherapy regimen. Given the paucity of data surrounding adjuvant T-mediated cardiotoxicity among the general population, we performed a retrospective review of cardiac toxicity among all patients receiving adjuvant T at the BCCA. Methods: Patients receiving adjuvant T between July 1, 2005 and December 31, 2005 either sequentially or concurrently with their primary chemotherapy regimen were identified by screening the BCCA pharmacy database. A chart review was conducted and the T start date; LVEF values at 0, 3 and 6 months; and patients with symptoms suggestive of congestive heart failure were identified. The mean LVEF values at 0, 3 and 6 months were calculated. Results: 133 patients received adjuvant T alone after completing their primary chemotherapy. The mean baseline LVEF was 60.5%. Of the 101 and 11 patients available for analysis at 3 and 6 months, the mean LVEF was 58.5% and 58.4%, respectively. 5 patients (3.8%) developed symptoms of CHF. 58 patients received adjuvant T concurrently with their primary chemotherapy (four cycles of AC followed by four cycles of concurrent paclitaxel and T). Of these, only 18 patients had an LVEF measured at 0 and 3 months, with a mean LVEF of 64.6% and 63.6%, respectively. Of the 7 patients who also had an LVEF measured at 6 months, the mean was 60.5% for an absolute decrease of 4.1% from baseline. One patient (1.7%) had symptomatic CHF. Conclusions: A clinically meaningful rate of cardiotoxicity is seen with both sequential and concurrent adjuvant T. In particular, we have demonstrated a higher rate of cardiotoxicity with adjuvant T alone than was observed in the HERA trial. These findings support ongoing stringent cardiac monitoring among the general population treated with adjuvant T. [Table: see text]

Patterns of adjuvant hormonal therapy (AHT) usage in early stage breast cancer (ESBC)

10695 Background: Aromatase inhibitors (AIs) are recommended as first line agents or after tamoxifen (T) as extended adjuvant therapy in hormone receptor positive ESBC. Little is known about adherence, adverse events, toxicity, duration of therapy, or change in agents in the community setting. Disparities between actual usage and clinical guideline recommendations could have a significant impact on outcomes. Methods: This retrospective observational study reviewed charts of 200 ESBC patients (pts) receiving AHT from 4 US community oncology clinics. To be eligible, each patient must have completed &gt;1 patient care monitor (PCM) survey, a validated electronic self-report measure that produces indices related to physical symptoms, psychological symptoms, functional status and overall health-related QOL. Baseline symptoms and toxicities prior to initiation of AHT and during and/or after are available on all evaluable patients. Pt charts were identified consecutively in reverse chronological order starting from 3/01/05. Results: Data are available on 42 pts. The mean age of the patients was 63.6 (range 43–86). First line AHT was T in 24 and AI in 18. Of available AIs, 14 pts received anastrozole, 3 letrozole and 1 exemestane. 18 pts continue AHT as per guidelines and 7 completed planned therapy (median duration, 58.8 months). Switching from 1st line AHT to another agent occurred in 13 pts; 10 switched from TAM to an AI, mean duration of TAM 31.0 months and 3 pts to another AI. 8 pts (19%) changed for an adverse event (AE), and 5 changed due to MD/pt preference. AEs included eye problems (2), weight changes (2), GYN complaints (2), vasomotor symptoms (1), muscle/joint aches (2), and increased alkaline phosphatase (1). Of pts receiving 2nd line AHT, 4 had discontinuation for an AE: muscle/joint aches (2), vasomotor symptoms (1), and eye problems (1). Conclusion: Switching of first line AHT is common for reasons of AEs or MD/pt decision. Pts with AEs to AHT often experience additional AEs after exposure to another agent. [Table: see text]

Follow-up for patients with breast cancer — who benefits? The surgeon's view

To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor–positive early-stage breast cancer.We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor–positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen.Assuming a no evidence of disease (NED)–PBI utility of 0.93, quality-adusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women.For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.

Emerging Data on Optimal Adjuvant Endocrine Therapy: Breast International Group Trial 1-98/MA.17

In recent years, several major trials have studied aromatase inhibitors (AIs)/inactivators as adjuvant therapy for postmenopausal women with early-stage breast cancer. The AIs have demonstrated improved efficacy compared with 5 years of tamoxifen when used as initial therapy or when used sequentially after 2-3 years. They also improve outcomes when used after 5 years of adjuvant tamoxifen in this patient population. In all cases, AIs improve disease-free survival compared with the standard 5 years of adjuvant tamoxifen, leading to a reassessment of the optimal adjuvant endocrine therapy for postmenopausal patients with breast cancer. The American Society of Clinical Oncology now recommends the inclusion of an AI into the adjuvant regimen at some point for most postmenopausal patients with hormone receptor—positive earlystage breast cancer. However, the optimal duration of AI therapy and the comparative efficacy and safety of the alternative strategies for their incorporation remain matters of debate. In addition, the long-term impact of AIs on other organs, such as the bone and cardiovascular systems, is not completely understood, and longer follow-up of patients from these original trials as well as carefully planned future trials with appropriate substudies are essential to determine the optimal endocrine treatment strategy.

The Impact of the Gene Recurrence Score on Chemotherapy Prescribing in ER Positive, Lymph Node Positive Early Stage Breast Cancer

The Impact of the Gene Recurrence Score on Chemotherapy Prescribing in ER Positive, Lymph Node Positive Early Stage Breast Cancer

19 The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

19 The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer