Breast Cancer Treatment Decisions Research Articles

A survey of breast cancer physicians regarding patient involvement in breast cancer treatment decisions

PurposeShared breast cancer treatment decision-making between patients and physicians increases patient treatment satisfaction and compliance and is influenced by physician-related factors. Attitudes and behaviors about patient involvement in breast cancer treatment decisions and treatment-related communication were assessed by specialty among breast cancer physicians of women enrolled in the Breast Cancer Quality of Care Study (BQUAL). ResultsOf 275 BQUAL physicians identified, 50.0% responded to the survey. Most physicians spend 46–60 min with the patient during the initial consult visit and 51.5% report that the treatment decision is made in one visit. Oncologists spend more time with new breast cancer patients during the initial consult (p = 0.021), and find it more difficult to handle their own feelings than breast surgeons (p = <0.001). ConclusionBreast surgeons and oncologists share similar attitudes and behaviors related to patient involvement in treatment decision-making, yet oncologists report more difficulty managing their own feelings during the decision-making process.

Changing ER, PgR, and HER2 status between primary and recurrent breast cancer.

92 Background: Estrogen receptor (ER), progesterone receptor (PgR), and HER2 status are important biological markers for making decisions about breast cancer treatments. Although changes of hormone receptor (HR) and HER2 status with recurrence of breast cancer are clinically experienced, the frequency of discordance and clinical significance are still unknown. Thus, we investigated ER, PgR, and HER2 status with primary tumors and recurrent lesions, and assessed discordance rates and prognosis. Methods: We retrospectively identified recurrent breast cancer patients who had biopsies or resections of recurrent lesions between January 2007 to April 2012 at Keio University Hospital. HR status was assessed by immunohistochemistry (IHC) and determined using the Allred score. HR status was defined as positive when score was 3 and more. HER2 status was assessed by IHC and fluorescence in situ hybridization (FISH) analysis. We defined HER2 positivity as 3+ staining intensity by IHC or the presence of HER2 gene amplification by FISH. Results: Among 32 recurrences, 40% (13) were loco-regional recurrences (LLR) and 60% (19) were distant metastases (DM) (lung 14; liver 3; brain 1; pleura 1). Discordance rates in ER, PgR and HER2 status between the primary tumors and the recurrence lesions were 12.5%, 31.3%, and 13.8%, respectively. The most common change was loss of PgR. Changings from negative to positive in ER, PgR and HER2 status were found in 6.3%, 3.1%, and 3.4% of the patients, respectively. All gains were found in distant metastases. Discordance in ER and HER2 were more common in DM (15.8% and 17.6%) comparing with LRR (7.7% and 8.3%). Loss of HR status was not associated with a shorter time to progression (TTP) (ER: 19.3 vs. 8.5 months, p=0.185; PgR: 4.4 vs. 11.5 months, p=0.907). Patients with discordant HER2 status had significantly shorter TTP than with concordant status (0.9 vs. 11.5 months, p=0.012). Conclusions: Discordance of biological markers between primary and recurrent breast cancers were seen in 10-30%. Although HR discordance was not associated with prognosis, patients with HER2 discordance had poorer TTP. Tissue confirmation should be considered for making effective treatment decisions in recurrent breast cancer.

Patient decision aids for cancer treatment

Although patient decision aids (pDAs) are effective, widespread use of pDAs for cancer treatment has not been achieved. The objectives of this study were to perform a systematic review to identify alternate types of decision support interventions (DSIs) for cancer treatment and a meta-analysis to compare the effectiveness of these DSIs to pDAs. The inclusion criteria for the study were: 1) all published studies using a randomized, controlled trial design, and 2) DSIs involving treatment decision-making for breast, prostate, colorectal, and/or lung cancer. For this analysis, DSIs were classified as pDAs if: 1) one reported outcome measure mapped onto the International Patient Decision Aids Standards Collaboration effectiveness criterion, and 2) the DSI was evaluated relative to standard consultation. Random effects models were used to compare the effectiveness of pDAs relative to other identified DSIs for reported outcomes. A total of 71 studies were reviewed, and 24 met the inclusion criteria. Overall, there were no significant differences in knowledge, satisfaction, anxiety, or decisional conflict scores between pDAs and other DSIs. This study showed that the effectiveness of other DSIs, including question prompt lists and audiorecording of the consultation, is similar to pDAs. This is important because it may be that these less complex DSIs may be all that is necessary to achieve similar outcomes as pDAs for cancer treatment.

P05.19. Outcomes in breast cancer treatment decision-making

Methods This case-control study involved telephone interviews at baseline, and completion of spirituality, self-efficacy, and control over treatment DM questionnaires at baseline, 6 months, and 1 year. Forty cases and 40 controls with stage 0-III breast cancer were matched by age, stage of illness, and province. Differences between pairs at each time point, adjusted for the time since diagnosis, were estimated using GEE linear regression models.

Improving the quality of breast cancer surgical treatment decisions.

6024 Background: Ensuring breast cancer treatment decisions are high quality (i.e., informed and preference-concordant) is a key component of patient centered care. Methods: A web-based decision tool, including an interactive preference clarification exercise, was developed over a one-year period with input from health communication experts, clinicians, and women with breast cancer. Newly diagnosed early stage breast cancer patients from two cancer centers were recruited and randomized to view the tool before or after completing a survey. Mean scores for key outcome measures, including surgical treatment knowledge (4 true/false questions), decision satisfaction (12 questions each with a 5-point Likert scale from strongly agree to strongly disagree), and preference-concordant decisions, were compared between the groups using t-tests. Concordance between preferences and surgical choices was evaluated using the chi-square test. Results: 110 subjects were recruited and 105 completed the study. Their mean age was 57 years, 60% had a college degree or more, and 81% were white. Those viewing the website first had higher scores on several decision outcomes than those taking the survey first (Table). Knowledge scores were also higher among those viewing the website before the survey (3.0 vs. 2.61, p=.23). The risk of recurrence was the most important treatment attribute, followed by retaining the natural breast, in both groups. Concordance between treatment choice and computer generated treatment was 65% for website first and 61% for survey first groups. Conclusions: A tool focused on improving knowledge and preference-concordant decisions produced positive results on breast cancer surgical treatment decision making. Further work should assess the impact of the tool in larger and more diverse populations. [Table: see text]

The involvement of partners in breast cancer treatment decision making.

6023 Background: Incorporating partners into treatment decision making is an important element of patient-centered care, yet little is known about the role of partners in the decision process. Methods: We surveyed 503 partners of a population-based sample of breast cancer survivor 4 years after diagnosis (RR= 76%, N=382).The outcome was partners’ reports of decision regret. Independent variables included decision making process measures (partners’ reports of sufficient treatment information receipt and sufficient involvement in decision making), race/ethnicity, age, education and income. Multivariable logistic regression was used to assess associations between decision regret and race/ethnicity, controlling for other variables. Results: 49% of partners were white, 14% African American, 15% more-acculturated Latino, and 18% less-acculturated Latino. One quarter (26%) of partners reported that they received insufficient information and one third (35%) desired more involvement in decision-making. Compared to whites, less-acculturated Latino partners more often reported that they received insufficient information (41% vs. 18%, p&lt;0.05) and desired more involvement in decision-making (49% vs. 14%, p&lt;0.001). Overall 30% of partners reported high decision regret. Multivariate analyses showed factors associated with high decision regret were less-acculturated Latinos, insufficient information receipt and desire for more involvement (Table). Conclusions: Most partners of breast cancer survivors reported low decision regret and positively appraised their involvement in the decision process. Less acculturated Latinos reported more dissatisfaction with the decision process. Findings suggest the need for culturally appropriate treatment decision support interventions that include partners. [Table: see text]

Abstract LB-305: Circulating tumor cells as a novel model to test efficacy of individualized therapy in breast cancer

Abstract Background: Recent reports suggest that circulating tumor cells (CTCs) mimic cancer progenitor cells, which are commonly resistant to various treatment modalities and are capable of invasion and tumor initiation at a single cell level. We hypothesized that CTCs isolated from metastatic breast cancer (MBC) patients can be propagated in 3-D in vitro systems, representing a clinically relevant model to study MBC biology and to test efficacy of multiple anti-cancer drugs. Methods: CTCs were isolated from MBC patient peripheral blood by depleting leucocytes and red blood cells. Enriched CTCs were immunostained for detection as CD45-negative (-) and nuclear counter stain-positive (+) cells, and for expression of estrogen receptor (ER) and HER-2. In order to obtain a large and continuous supply of CTCs for our culture studies, we screened 19 primary transplantable xenograft lines, established by directly transplanting human breast tumors into epithelium-free mammary fat pads of SCID/Beige mice, for their production of CTCs. The CTCs were isolated together with mouse mononuclear blood cells by either gradient centrifugation or red blood cell lysis, and identified by human pan-cytokeratin immunostaining. Viable CTCs isolated from both patients and xenograft mice were plated in mammosphere conditions either alone or in co-culture with mammary fibroblasts tagged with green fluorescent protein (GFP). the propagated CTCs were identified as GFP-, cytokeratin 19+ cells. Results: To date, we have collected and processed blood samples from 14 MBC patients. CTCs were detected in 5 out of the 8 samples (62%) already analyzed. Interestingly, in 2 out of 4 patients (50%) with positive CTC counts and ER+ primary tumor, all the isolated CTCs were ER-. Moreover, we found HER-2+ CTCs in 1 out of 4 patients (25%) with HER-2 negative disease. CTC count and characterization of the additional collected samples is ongoing and will be presented at the conference. In the mice bearing primary xenografts, we detected CTCs in 13 out of 19 lines (68%) and in 26 out of 54 mice (48%). When CTCs isolated from either human patients or primary xenografts were cultured alone, no mammospheres were observed. In contrast, when CTCs were cultured in direct contact with fibroblasts we observed the formation of mixed CTC/fibroblast spheres that may reproduce the tumor cell/stroma interaction observed in vivo. Moreover, in the presence of GFP+ fibroblasts, the numbers of GFP- cells and cell aggregates were clearly higher at all time points compared to the single culture. Conclusions: Our study suggests that viable CTCs isolated from human patients and primary xenograft bearing mice can be propagated in vitro in presence of mammary fibroblasts. The successful development of a CTC-based cell culture platform will provide a unique model to better understand the biological mechanisms of the metastatic process and to guide treatment decisions in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-305. doi:1538-7445.AM2012-LB-305

Abstract 5497: Breast cancer treatment decision-making: Are we asking too much of patients

Abstract Background. Physicians are mandated to offer treatment choices to breast cancer patients yet not all patients may want the responsibility that entails. Prior studies show that breast cancer patients who are not given enough responsibility for treatment decision-making have poorer treatment knowledge and report worse quality of care. In contrast, few studies explore potential adverse consequences for breast cancer patients who feel they are given too much responsibility for treatment decision-making. Methods. We sought to describe and compare women by degree of responsibility they felt they had for making decisions about their breast cancer treatment. Our sample includes women with early-stage breast cancer treated surgically at 8 NYC hospitals, recruited for an RCT of patient assistance to improve receipt of adjuvant treatment. In multivariable analyses, we explored the association between treatment decision-making responsibility and a) baseline knowledge of benefit of surgical and adjuvant treatments discussed with doctor and b) regret of treatment decisions after 6 months. Results. Of 368 women aged 28-89y enrolled at baseline, 72% reported a “reasonable amount,” 21% “too much,” and 7% “not enough” responsibility for treatment decision-making. The majority in the first group were White (53%), earned &amp;gt;$150,000/year (33%), completed college (53%), had no health literacy problems (50%), and had a great deal of self-efficacy (61%). In contrast, the majority with “not enough” responsibility were Black (42%), earned &amp;lt;$50,000/year (58%), did not finish high school (39%), had health literacy problems (68%), and had low self-efficacy (69%). The majority with “too much” responsibility were Hispanic (68%), earned &amp;lt;$15,000/year (54%), did not finish high school (37%), and had health literacy problems (62%), despite having a great deal of self-efficacy (64%). Only 29% of women had knowledge of treatment benefits and 40% experienced decision regret at 6 months. Multivariable analysis found that women with “too much” vs. a “reasonable amount” of responsibility had less treatment knowledge ([OR] 0.46 [95% CI] 0.21, 0.99; model c=0.7301; p&amp;lt;0.001) and more decision regret at 6 months ([OR] 3.16 [CI] 1.59, 6.29; model c=0.7821; p&amp;lt;0.001). The few women with “not enough” responsibility also had less treatment knowledge, and more decision regret, though results were not statistically significant in this small group ([OR] 0.74 [CI] 0.23, 2.37 and [OR] 3.26 [CI] 0.93, 11.4). Conclusion. Overall, treatment knowledge is low and decision regret common in this group of breast cancer patients. Among women with “too much” responsibility for treatment decisions, low health literacy is common and this has important negative consequences. Physicians must find different ways to communicate with low health literacy patients to enable breast cancer patients to achieve adequate levels of treatment decision responsibility and reduce decision regret. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5497. doi:1538-7445.AM2012-5497

Impact of axillary ultrasound and core needle biopsy on the utility of intraoperative frozen section analysis and treatment decision making in women with invasive breast cancer

BackgroundOur objective was to evaluate the impact of preoperative axillary ultrasound and core needle biopsy (CNB) on breast cancer treatment decision making. A secondary aim was to evaluate the impact on the utility of intraoperative sentinel lymph node (SLN) frozen section. MethodsA review of 84 patients with clinically negative axilla who underwent axillary ultrasound was performed. Sensitivity, specificity, and positive/negative predictive value for axillary ultrasound with CNB was calculated. ResultsThirty-one (37%) had suspicious nodes. Of 27 amenable to CNB, 12 (14%) were malignant, changing treatment plans. The sensitivity of ultrasound and CNB was 54% and specificity 100%; the positive and negative predictive values were 100% and 80%, respectively. In 41 patients with normal ultrasounds who underwent SLN frozen section, 10 (24%) were positive. ConclusionsPreoperative axillary ultrasound impacts treatment decision making in 14%. With a sensitivity of 54%, it is a useful adjunct to, but not replacement for, SLN biopsy. Frozen section remains of utility even after a negative axillary ultrasound.

Factors Noted to Affect Breast Cancer Treatment Decisions of Women Aged 80 and Older

To identify factors that influence the breast cancer treatment decisions of women aged 80 and older. Medical record review. One academic primary care clinic and two community health centers in Boston. Sixty-five women aged 80 and older diagnosed with breast cancer between 1994 and 2004 and followed through June 30, 2010. Data were abstracted on breast cancer characteristics, comorbidities, treatments received, and outcomes. Notes from primary care physicians, oncologists, and breast surgeons were reviewed to determine factors involved in treatment decision-making. Median age at diagnosis was 84.0 (interquartile range 82.0-86.3), 55 (84.6%) were non-Hispanic white, and 40 (61.5%) had at least one comorbidity. Nine women were diagnosed with ductal carcinoma in situ, 42 with a new primary invasive breast cancer, eight with a second primary, and six with a breast cancer recurrence. Sixty-three (96.9%) received some type of treatment. Fifty-six (86.2%) had at least one detailed physician note on treatment decision-making in their charts. The main categories found to influence participant, family, and physician treatment decision-making were tumor characteristics, ratio of treatment benefits to risks, logistics (e.g., transportation, finances), and participant age, health (including a concurrent diagnosis), and psychosocial characteristics. Family was involved in treatment discussions for 46 (70.8%) participants. The quality of physician documentation about decision-making in these women was high. A great amount of thoughtful and complex decision-making involving patients, family, and physicians occurs after a woman aged 80 and older is diagnosed with breast cancer.

Breast cancer treatment decision making among Latinas and non-Latina whites: A communication model predicting decisional outcomes and quality of life.

Deciding among medical treatment options is a pivotal event following cancer diagnosis, a task that can be particularly daunting for individuals uncomfortable with communication in a medical context. Few studies have explored the surgical decision-making process and associated outcomes among Latinas. We propose a model to elucidate pathways through which acculturation (indicated by language use) and reports of communication effectiveness specific to medical decision making contribute to decisional outcomes (i.e., congruency between preferred and actual involvement in decision making, treatment satisfaction) and quality of life among Latinas and non-Latina White women with breast cancer. Latinas (N = 326) and non-Latina Whites (N = 168) completed measures six months after breast cancer diagnosis, and quality of life was assessed 18 months after diagnosis. Structural equation modeling was used to examine relationships between language use, communication effectiveness, and outcomes. Among Latinas, 63% reported congruency in decision making, whereas 76% of non-Latina Whites reported congruency. In Latinas, greater use of English was related to better reported communication effectiveness. Effectiveness in communication was not related to congruency in decision making, but several indicators of effectiveness in communication were related to greater treatment satisfaction, as was greater congruency in decision making. Greater treatment satisfaction predicted more favorable quality of life. The final model fit the data well only for Latinas. Differences in quality of life and effectiveness in communication were observed between racial/ethnic groups. Findings underscore the importance of developing targeted interventions for physicians and Latinas with breast cancer to enhance communication in decision making.

Abstract A31: A patchwork of life: A bilingual breast cancer treatment patient decision aid targeted at medically underserved women

Abstract Introduction: Most patient decision aids rely heavily on written information and require patients to have above average literacy skills, a potential barrier for the medically underserved. Individuals with limited literacy are restricted in their ability to make appropriate health decisions and to act on health information. We developed and evaluated the “A Patchwork of Life” (PLife) patient decision aid to assist medically underserved women with limited literacy in making a breast cancer treatment decision. The PLife is computer-based, culturally and linguistically appropriate learning environment that involves two key components, soap opera segments and related learning modules designed to support breast cancer (Stages I-IIIA) surgery decision-making and to encourage communication about treatment decision with their provider, relatives and friends. The objectives of the project were to: 1) determine the effectiveness of PLife in assisting patients make informed breast cancer treatment decisions, and; 2) evaluate patients’ perceptions of the usefulness of the intervention for aiding in their decision-making. Experimental Procedures: The study was a randomized controlled trial including an intervention and control group. The intervention group viewed the PLife program and the control group received usual care including additional breast cancer educational material provided by the National Cancer Institute (NCI). Both groups consisted of patients who were candidates for lumpectomy or mastectomy. Patients were identified through pathology and other medical records and physician referrals. Those who consented completed all baseline assessments before implementation of the PLife decision aid. A Patient Navigator arranged for a convenient time for the patient to view the program. Immediately after viewing the program, patients answered a questionnaire rating the program. Follow-up data collection with patients took place via phone 2-weeks after viewing the program. At 2-week, and 6-month follow up patients answered questions about breast cancer knowledge, decisional conflict, and treatment preferences. Questionnaires were administered in Spanish and English. Summary of Data: A total of 100 patients diagnosed with Stage I-IIIA breast cancer were randomized to either a control (n = 49) or intervention group (n = 51). Median age of the sample was 49 ± 11.6 years, 15% were Non-Hispanic White, 56% African American, and 49% Hispanic. The majority of patients chose mastectomy over lumpectomy, regardless of study group assignment (60.8% intervention vs 53.1% control). Intervention group exhibited greater improvement in breast cancer knowledge compared to control group (60.5% vs 37.7%, respectively). At six month follow-up, patients who viewed the PLife program felt more informed about their treatment options, risks and benefits (p = 0.01), and showed significant improvement in decision certainty about breast cancer treatment (p = 0.01) compared to control group. Usability analysis revealed a high level of user satisfaction with the PLife program. Conclusions: Results suggest that the PLife program improved patients’ knowledge about breast cancer. Additionally, patients who interacted with the PLife program exhibited an overall greater treatment decision certainty compared to usual care group. Taken together, these findings suggest, that the PLife program is a suitable strategy to help medically underserved women with breast cancer maximize their understanding of the implications of breast cancer treatment options. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A31.

Abstract A32: Implementing a breast cancer treatment patient decision aid in a medically underserved population in Texas

Abstract Background: Decision aids are designed to help patients make informed decisions about medical treatment options. We developed and evaluated the effectiveness of culturally and linguistically appropriate breast cancer patient decision aid, “A Patchwork of Life” (PLife), targeted at medically underserved women with limited literacy. The PLife is a computer-based learning environment that involves two key components, soap opera segments and related learning modules designed to support breast cancer (Stages I-IIIA) surgery decision-making and to encourage communication about treatment decision with their provider, relatives and friends. The objectives of the current project are to implement the Plife program at one of the National Community Cancer Center Program (NCCCP) sites, in Austin Texas to: 1) evaluate the effectiveness of the implementation of the PLife program at the NCCCP clinic site by conducting an assessment of program outcomes with various stakeholders – patients, physicians, and patient navigator; 2) evaluate patients’ and providers'perceptions of the usefulness of the intervention for aiding in their decision-making. Experimental Procedures: We will recruit 60 patients diagnosed with Stage I-IIIA breast cancer over 18 months. Patients will be identified through pathology and other medical records and physician referrals. Those who consent will complete all baseline assessments before implementation of the PLife decision aid. A Patient Navigator will arrange for a convenient time for the patient to view the program. Immediately after viewing the program, patients will answer a questionnaire rating the program. Follow-up data collection with patients will take place via phone 2-weeks after viewing the program. Measures to be collected at the 2-week follow up include breast cancer knowledge, decisional conflict, and treatment preferences, and provider perception questionnaires. Questionnaires will be administered in Spanish and English. Expected Results and Conclusions: The proposed project will enable the NCCCP site to significantly enhance breast cancer education, awareness and navigation for the underserved breast cancer patients who currently do not receive education or navigation services utilizing a tool that has been proven to assist patients with limited literacy in making informed breast cancer treatment decisions. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A32.

The impact of physicians' reactions to uncertainty on patients' decision satisfaction

Patients' and physicians' response to uncertainty may affect decision outcomes. The purpose of this study was to explore the impact of patients' and physicians' reactions to uncertainty on patients' satisfaction with breast health decisions. Seventy-five women facing breast cancer prevention or treatment decisions and five surgeons were recruited from a breast health centre. Patients' and physicians' anxiety from uncertainty was assessed using the Physicians' Reactions to Uncertainty Scale; wording was slightly modified for patients to ensure the scale was applicable. Patients' decision satisfaction was assessed 1-2 weeks after their appointment. A mixed-effects logistic regression model was used to assess associations between patients' and providers' anxiety from uncertainty and patients' decision satisfaction. A provider-specific random effects term was included in the model to account for correlation among patients treated by the same provider. Patients' decision satisfaction was associated with physicians' anxiety from uncertainty (beta = 0.92, P < 0.01), but not with patients' anxiety from uncertainty (beta = -0.18, P > 0.27). This study suggests that physicians' reactions to uncertainty may have an effect on decision satisfaction in patients. More research is needed to confirm this relationship and to determine how to help patient-provider dyads to manage the uncertainty that is inherent in most cancer decisions.

Relationship of ER, PR, and HER2-neu status with age, menopausal status, and axillary nodal status in early breast cancer.

e11011 Background: Treatment decisions in early breast cancer are mostly based on age, menopausal status, tumor size, axillary nodal status, hormone receptors status and Her 2 neu expression. Correlation of ER, PR and Her 2 neu expression with other clinical parameters of disease is not clearly defined. This study attempts to identify the relationship of ER, PR and Her 2 neu status with age, menopausal and axillary nodal status. Methods: Data on ER, PR and Her 2 neu expression status of 289 consecutive early breast cancer patients treated during 2008-2010 in Mayo Hospital Lahore was obtained. Relationship of ER, PR and Her 2 neu status with these parameters of disease was studied by finding correlation co efficient. SPSS version 11.5 was used for statistical analysis. Results: HER2 over expression (3+ by IHC or by FISH) was seen in 125/289 (43.25 %), hormone receptor positivity (ER/PR or both) in 133/289 (46.02 %) and 88 patients (30.4 %) were triple negative. Majority of triple negative patients 69/88 (78.4 %) were pre menopausal with a median age of 43.8 years (range; 25-72) and median size of primary of 5.2 cm (range;2-12 cms). Half of these patients were node -ve (44/88) and in remaining patients median number of 2.4 nodes (range; 0-18). Triple negative disease was negatively related to age of patients (r = - 0.75). HER2 +ve / receptor -ve patients were 68 (23.52 % ) and 41 (60.29 %) patients were pre menopausal with a median age of 50.5 years (range; 28-85) and median size of primary of 4.5 cm (range; 1.5-12.5 cms). Fifty patients (73.53%) were node positive with a median number of 4.5 nodes (range;0-23). 133 receptor +ve patients (either ER or PR or both) had an associated Her 2 neu over expression in 57/133. Eighty six patients (64.66 %) were pre menopausal with a median age of 47 years (range; 25-90) and median size of primary of 4.48 cm (range; 1-18 cms). 91patients (68.42 %) were node +ve with a median number of 3.71 nodes (range;0-19). Conclusions: ER, PR and Her 2 neu status doesn’t correlate with clinical parameters of disease. Triple negative, Her 2 enriched or receptor positive molecular subtypes of disease cannot be predicted from clinical parameters. However, triple negative disease tends to be frequent in younger patients.

HER2 Evaluation and Its Impact on Breast Cancer Treatment Decisions

Background: Eighteen to twenty percent of breast cancer tumors show abnormal amplification of the Human Epidermal growth factor Receptor 2 (HER2) gene and increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation and shorter disease-free and overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about use of HER2 testing in real-world settings. This study examined uptake, use, appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions. Methods: We assessed electronic data from 3,634 patients with invasive breast cancer diagnosed from 1998 to 2007 in a large integrated health system. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment. Results:From 1998 to 2000, the percent of patients who underwent HER2 evaluation increased from 12 to 94%; <3% of women with ductal carcinoma in situ, for whom HER2 testing is not recommended, were tested. Trastuzumab use increased 5-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. Conclusions:These findings illustrate appropriate and effective implementation of a HER2 testing strategy in a managed care setting.

Abstract P6-10-07: Risk-Benefit Framework To Evaluate Gene-Expression Profiling in Early Stage Breast Cancer: A Decision Model Developed in Collaboration with Stakeholders

Abstract Objectives Recent comparative effectiveness research recommendations have emphasized that stakeholder involvement in research prioritization and design is critical for ultimate acceptance of results. With this recommendation in mind, an interactive risk-benefit model was developed to evaluate gene-expression profiling (GEP) to guide use of adjuvant chemotherapy in early stage breast cancer compared to clinical guidelines. Methods A stakeholder collaborative feedback process was utilized to develop a decision model to estimate the comparative benefits and harms of GEP relative to NCCN guidelines, including disease recurrences, adverse events, and quality-adjusted life years (QALYs). The model allows users to specify the GEP, node status, patient cohort age, adjuvant chemotherapy relative risk reduction, and patient chemotherapy preferences in each risk stratum. A Markov process was utilized to estimate long-term clinical outcomes. Based on stakeholder concerns about QALY-based outcomes, alternative outcomes such as disease recurrences and adjuvant chemotherapy serious adverse events were presented. The prognostic and predictive properties of the GEPs were derived from published retrospective analyses of RCTs. Adjuvant chemotherapy utility decrements were derived from trial-based adverse event rates. The base case patient was a pre-menopausal woman of age 44. Results Preliminary analyses indicate that a 2-risk strata GEP, 3-risk strata GEP, and clinical guidelines would identify 50%, 46% and 92% of women to receive adjuvant chemotherapy, respectively. Based on this level of uptake, relative to a scenario where no patients receive adjuvant chemotherapy, these prognostic approaches would prevent 29%, 36% and 34% of distant recurrences, respectively. This scenario results in 17.4 QALYs, 18.1 QALYs, and 17.7 QALYs, respectively. These findings indicate that depending on the specific GEP examined, testing may lead to a net harm or net benefit relative to clinical guidelines, due to variation in risk of disease recurrence, despite avoidance of chemotherapy and side effects in 42% and 46% of women, respectively. Conclusions GEP to inform adjuvant chemotherapy treatment decisions in early stage breast cancer could lead to an increase or decrease in QALYs relative to the use of clinical guidelines, depending on the specific GEP examined. Stakeholder feedback has indicated that acceptance of model results will likely depend on its degree of transparency, ease of use and interpretation, and ability to present relevant outcome measures. Ongoing efforts are focused on additional collaboration with stakeholders to align model structure and output with current needs. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-10-07.

Abstract P3-12-12: HER2 Evaluation in Relation to Breast Cancer Treatment Decisions in a Managed Care Plan

Abstract Background: In 18-20% of breast cancer tumors, the human epidermal growth factor receptor 2 (HER2) gene is abnormally amplified with increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation, shorter disease-free survival, and poorer overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about HER2 testing practices and associated treatment in real-world settings. This study examined uptake, use, and appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions in a large integrated health system. Methods: We identified 3,634 patients with primary breast cancer diagnosed from 1998-2007 who were members of the Kaiser Permanente Northwest health plan. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment from tumor registry and pharmacy datasets. We defined women as evaluated for HER2 if they received HER2 testing by immunohistochemistry (IHC) and/or fluorescent in-situ hybridization (FISH). We manually abstracted medical charts for a subset of patients to verify findings and investigate anomalies. We compared testing and treatment results to professional guidelines. Results: From 1998-2000, the percentage of patients with invasive breast cancer who underwent HER2 evaluation increased from 12% to 94%; from 2000-2007, 94% (2304/2461) received HER2 testing over all years combined. In most cases, an equivocal or positive IHC test was followed by FISH. Only 2.4% of women with ductal carcinoma in situ (13/538), for whom HER2 testing is not recommended, were tested, and the proportion remained consistently low over the entire study period. Trastuzumab use increased five-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result, while the remainder had equivocal HER2 results or received treatment outside thedelivery system. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. We estimate that, after correcting for errors in the datasets, professional guidelines were followed for over 97% of patients diagnosed since 2000. Conclusions: Kaiser Permanente Northwest is systematically performing HER2 evaluation on patients with invasive breast cancer, and the information is used to make appropriate treatment decisions. This information should be gathered in other health care settings for comparison. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-12.

Development of instruments to measure the quality of breast cancer treatment decisions

Women with early-stage breast cancer face a multitude of decisions. The quality of a decision can be measured by the extent to which the treatment reflects what is most important to an informed patient. Reliable and valid measures of patients' knowledge and their goals and concerns related to breast cancer treatments are needed to assess the decision quality. To identify a set of key facts and goals relevant to each of three breast cancer treatment decisions (surgery, reconstruction and adjuvant chemotherapy and hormone therapy) and to evaluate the validity of the methods used to identify them. Candidate facts and goals were chosen based on evidence review and qualitative studies with breast cancer patients and providers. Cross-sectional surveys of patients and providers were conducted for each decision. The accuracy, importance and completeness of the items were examined. Thirty-eight facts (11-14 per decision) and 27 goals (8-10 per decision) were identified. An average of 17 patients and 21 providers responded to each survey. The sets of facts were accurate and complete for all three decisions. The sets of goals and concerns were important for surgery and reconstruction, but not chemotherapy/hormone therapy. Patients and providers disagreed about the relative importance of several key facts and goals. Overall, breast cancer patients and providers found the sets of facts and goals accurate, important and complete for three treatment decisions. Because patients' and providers' perspectives are different, it is vital that instrument development should include items reflecting both views.

Multigene assays and isolated tumor cells for early breast cancer treatment: time for bionetworks

Despite advances with adjuvant endocrine treatment for hormone receptor-positive tumors and with trastuzumab for HER2-positive disease, overall, over 50% of women with early-stage breast cancer experience recurrence and die of the disease. Biomarkers for tailoring systemic adjuvant treatment to responder patients are needed. The multigene assays, 21-gene recurrence score (Oncotype DX® [Genomic Health, CA, USA]) and 70-gene signature (MammaPrint™ [Agendia, CA, USA]), and the isolated tumor cells in sentinel lymph node(s) represent the latest advances for improving adjuvant chemotherapy decisions. This article evaluates how these new markers, added to current standard factors (age, tumor size, grade, hormone receptor status and HER2 status), could improve early breast cancer treatment decisions. Moreover, emerging evidence from the latest large-scale studies using next-generation DNA-sequencing technology reveals a high heterogeneity and complexity of breast cancer. This assessment now shapes a new research strategy towards completion of a breast cancer causal (driver) mutations catalog and understanding complex genetic interactions and signaling pathway networks. Despite multiple challenges, advances in cancer genomes and systems biology approaches promise the future development of robust biomarkers.