Karleen Habin

Analysis of the MammaPrint Breast Cancer Assay in a Predominantly Postmenopausal Cohort

Purpose: Most node-negative breast cancer patients are older and postmenopausal and are increasingly being offered adjuvant chemotherapy despite their low overall risk of distant relapse. A molecular diagnostic test with high negative predictive value (NPV) for distant metastasis in this subgroup would spare many older breast cancer patients adjuvant treatment. Experimental Design: We determined the NPV and positive predictive value of the MammaPrint assay in breast cancer patients who were consecutively diagnosed and treated at the Massachusetts General Hospital between 1985 and 1997. Primary tumors from 100 patients with node-negative, invasive breast cancer (median age, 62.5 years; median follow-up, 11.3 years) were subjected to MammaPrint analysis and classified as being at either low or high risk for distant metastasis. Results: The MammaPrint 70-gene signature displayed excellent NPV as in previous studies, correctly identifying 100% of women at low risk for distant metastases at 5 years. However, this assay had a lower positive predictive value (12% at 5 years) than previously observed. Conclusions: The MammaPrint assay was originally designed to identify younger breast cancer patients at low risk for distant metastasis, who might consequently be spared systemic treatment. We show here that the same signature has a very high NPV for distant recurrence after adjuvant treatment in older breast cancer patients.

Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial.

Objective: Hot flashes are a major quality-of-life issue for breast cancer survivors, interrupting sleep, reducing quality of life, and diminishing treatment adherence to adjuvant endocrine therapies. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are used widely but are only partially effective for hot flashes. Alternative strategies are needed. We hypothesized that augmentation of SSRI/SNRI therapy with hypnotic agents would optimize hot flash therapy by improving sleep and quality of life. Methods: Women with breast cancer or at high risk for developing the disease who had hot flashes in association with nocturnal awakenings were randomized to double-blinded treatment with zolpidem 10 mg or placebo for 5 weeks. SSRI/SNRI nonusers (81%) started venlafaxine XR 75 mg/day concurrently, whereas SSRI/SNRI users continued that therapy. We compared the proportion of responders, defined as study completers with improved subjective sleep quality (Pittsburgh Sleep Quality Index) and/or objectively assessed wake time after sleep onset on actigraphy, between groups. Results: Of 53 women (aged 51 ± 8 y) randomized to zolpidem augmentation (n = 25) or placebo augmentation (n = 28), 38 completed the protocol (57% on placebo, 88% on zolpidem). More women augmented with zolpidem than placebo were responders on the sleep outcome (40% vs 14%; P = 0.035). Quality of life improved more with zolpidem than with placebo (P = 0.01). Treatment effects on hot flashes and mood did not differ between groups. Conclusions: Augmentation of SSRI/SNRI with zolpidem improves sleep and quality of life in breast cancer survivors with hot flashes and associated sleep disturbance. Adding a hypnotic agent to an SSRI/SNRI helps women to sleep through nighttime hot flashes. Treatments targeting sleep may be an important supplemental strategy to optimize well-being.

Applying a Conceptual Model for Examining Health-Related Quality of Life in Long-Term Breast Cancer Survivors: CALGB Study 79804

Objectives: The Survivors Health and Reaction study used a quality‐of‐life model adapted for cancer survivors by Dow and colleagues to identify factors related to global health‐related quality of life (HRQL) and to document the prevalence of problems and health‐oriented behaviors in a follow‐up study of breast cancer patients who participated in CALGB 8541.

P3-16-05: A Phase II Trial Expansion Cohort of the PARP Inhibitor Veliparib (ABT888) and Temozolomide in BRCA1/2 Associated Metastatic Breast Cancer.

Background: Veliparib (ABT-888) is a novel oral inhibitor of Poly (ADP-Ribose) Polymerase (PARP) 1 and 2. Veliparib and temozolomide (TMZ) are synergistic in breast cancer xenograft models. We recently conducted a phase II study of TMZ and veliparib in 41 patients (pts) with metastatic breast cancer (MBC). Activity was observed only in pts with known BRCA1 or BRCA2 deleterious mutations, with a response rate (RR) of 50% (4/8) and clinical benefit rate (CBR) of 62.5%. In order to further evaluate the activity and safety of TMZ and veliparib, we enrolled an expansion cohort of 20 additional patients with BRCA1 or 2 mutations. Methods: We previously conducted a single arm phase II trial of veliparib and TMZ in 41 MBC pts. Eligibility included measurable disease, ≥1 prior MBC therapy and PS ≤ 2. Available archived tumor samples were collected. In this expansion cohort, first line therapy for MBC and prior PARP inihibitor therapy were allowed, and eligible patients were required to have a known deleterious BRCA1 or BRCA2 mutation identified from prior clinical testing. The dose of veliparib in the original cohort was reduced from 40 mg PO BID to 30 mg PO BID. In the expansion cohort all patients received veliparib (30 mg PO BID days 1–7) and TMZ (150mg/m2 PO QD days 1–5) on a 28 day cycle. RECIST response was evaluated every 2 cycles. The primary endpoint was overall response rate. Secondary endpoints included PFS, OS, safety and toxicity. Results: Between June 24, 2010 and Sept 29, 2010, 20 eligible pts (median age 42) were enrolled. Baseline characteristics included: median PS=0 (range 0–2); 9 BRCA1 carriers, 9 BRCA2 carriers, and 2 unknown. 17 pts (85%) received prior adjuvant chemotherapy. 9 patients received a prior platinum chemotherapy. The most common grade 3/4 toxicities included thrombocytopenia and neutropenia. Best response for the 20 patients evaluable at the time of abstract submission includes 3 PR (15%), 6 SD (30%), 11 PD, and a clinical benefit rate of 45%. Combined with the initial cohort of 8 known carriers from the original 41 patients, the total RR is 25% (7/28) and clinical benefit rate of 50% (7 PR, 7 SD). The RR was 40% (6/15) in pts without prior platinum treatment, and 9% (1/11) in pts with prior platinum treatment. The median PFS for the 20 BRCA carriers was 85 days, and among patients with prior platinum treatment compared to no prior platinum, the median PFS was 70 and 179 days, respectively. Three pts remain on study, 1 with a CR for >20 mo. Discussion: We previously demonstrated that veliparib and TMZ is an active combination in BRCA1/2 associated MBC. In this larger expansion cohort of 20 additional patients, the combination continued to show activity, although the response rate was not as robust as previously observed. Differences between the original cohort and the expansion cohort may account for some variation in response, such as prior platinum or PARP inhibitors therapy, number of lines of prior therapy, and the dose of veliparib used (40mg vs 30 mg). These results support further evaluation of this regimen in the BRCA1/2 carrier population, and provide the opportunity to evaluate potential factors that may predict response or resistance to this regimen. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-05.

Aromatase inhibitors and musculoskeletal pain in patients with breast cancer.

Aromatase inhibitors are recommended for use by postmenopausal women who have estrogen receptor-positive early-stage breast cancer. They reduce local and distant recurrence more effectively than tamoxifen. Anastrozole (Arimidex, AstraZeneca Pharmaceuticals LP), letrozole (Femara, Novartis Pharmaceuticals Corporation), and exemestane (Aromasin, Pfizer Inc.) inhibit aromatase activity, thus significantly decreasing estrogen production in tissues such as liver, muscle, and fat. Very low levels of estrogen may be one cause of musculoskeletal pain, a common side effect associated with the drugs. In the major adjuvant aromatase inhibitor clinical trials, 25%-30% of the patients enrolled experienced musculoskeletal pain. Although quality-of-life studies demonstrate that aromatase inhibitors are well tolerated overall, some women discontinue this treatment because of musculoskeletal pain. Little is known about how to predict, measure, or manage musculoskeletal pain caused by aromatase inhibition. Oncology nurses play an important role in the assessment and management of side effects related to cancer. This article provides an overview of the current knowledge about musculoskeletal pain in patients with breast cancer receiving aromatase inhibitor therapy.

Women's experiences with antiestrogen therapy to treat breast cancer.

PURPOSE/OBJECTIVES To understand the experiences of women undergoing antiestrogen therapy (AET) to treat breast cancer. RESEARCH APPROACH Content analysis of tape-recorded focus group interviews. SETTING Breast oncology center of a large medical center in the northeastern United States. PARTICIPANTS Purposive sample of 21 women undergoing AET to treat breast cancer. METHODOLOGIC APPROACH A nonexperimental qualitative, descriptive design using open-ended interviews and content analysis to isolate themes. MAIN RESEARCH VARIABLES Womens experiences with AET. FINDINGS Five themes were isolated and were focused on the overall experience of having breast cancer: symptoms related to AET, shared decision making, being strong for others, discovering new priorities, and recognizing vulnerability. CONCLUSIONS Oral therapies are an increasingly popular treatment option for various types of cancer, particularly in women with estrogen-sensitive breast cancer. Although this type of treatment has been efficacious in terms of disease-free and overall survival, women undergoing AET face many challenges related to treatment. Healthcare providers need to understand womens perceptions of AET and its effects as a first step in the process of developing interventions to improve care. INTERPRETATION More research is needed to distinguish whether the presence of preexisting chronic illness, differences in type of AET, age, and ethnicity impact the overall experience of women on AET. Individual interviews may be necessary to fully explore the experience. Oncology nurses should implement surveillance care to explore the effects of AET on women with breast cancer.

Perceptions of Cancer Risk, Cause, and Needs in Participants from Low Socioeconomic Background at Risk for Hereditary Cancer

ABSTRACT The purpose of this study was to describe perceptions of cancer risk, cause, and needs in participants from a low socioeconomic background at risk for hereditary cancer. We surveyed 307 individuals with the Cancer Awareness and Needs survey and received 128 responses (41.6% response rate). Family history, genetics, and tobacco use were selected most frequently as a cause of cancer; 36% (n = 46) selected fate and/or Gods will. A total of 87.5% (n = 112) understood that having a close family member with breast cancer could increase personal risk; however responses were varied when asked if this was related to risk for other cancers. Most participants had undergone cancer screening, half reported undergoing breast magnetic resonance imaging, which was associated with personal (p < 0.01) and family cancer history (p = 0.03). An additional 76.6% (n = 98) felt informed about cancer screening and most received information from health care providers and family or friends. Ensuring that patients and clinicians are educated about hereditary cancer risk, detection, and prevention should be priorities for future research.

Disparities in Cancer Genetic Risk Assessment and Testing

Scientific and technologic advances in genomics have revolutionized genetic counseling and testing, targeted therapy, and cancer screening and prevention. Among younger women, African American and Hispanic women have a higher rate of cancers that are associated with hereditary cancer risk, such as triple-negative breast cancer, which is linked to poorer outcomes. Therefore, genetic testing is particularly important in diverse populations. Unfortunately, all races and ethnic groups are not well represented in current genetic testing practices, leading to disparities in cancer prevention and early detection.

Cancer Genetics and Genomics: Essentials for Oncology Nurses

Cancer genetics and genomics are rapidly evolving, with new discoveries emerging in genetic mutations, variants, genomic sequencing, risk-reduction methods, and targeted therapies. To educate patients and families, state-of-the-art care requires nurses to understand terminology, scientific and technological advances, and pharmacogenomics. Clinical application of cancer genetics and genomics involves working in interdisciplinary teams to properly identify patient risk through assessing family history, facilitating genetic testing and counseling services, applying risk-reduction methods, and administering and monitoring targeted therapies.

A state‐wide initiative to promote genetic testing in an underserved population

Genetic testing for cancer susceptibility has been widely studied and utilized clinically. Access to genetic services in research and practice is largely limited to well‐insured, Caucasian individuals. In 2009, the Cancer Resource Foundation (CRF) implemented the Genetic Information for Treatment Surveillance and Support (GIFTSS) program to cover the out‐of‐pocket expenses associated with cancer genetic testing, targeting high‐risk individuals with limited financial means and limited health insurance coverage. Here, we (i) describe the characteristics of participants in the Massachusetts (MA) GIFTSS program and (ii) evaluate mutations found in this diverse sample. A secondary retrospective data analysis was performed using de‐identified demographic data obtained from laboratory requisition forms and cancer genetic testing result information from the laboratory source. Eligible participants were those who utilized the MA GIFFTS program from 2009 through December of 2014. Data were summarized using descriptive measures of central tendency. Participants were residents of Massachusetts who had health insurance and had a reported income within 250–400% of the federal poverty level. Genetic testing results were categorized following clinical guidelines. Overall, 123 (13%) of participants tested positive for a mutation in a cancer susceptibility gene. For those with a cancer diagnosis, 65 (12%) were found to have a positive result and 20 (7%) had a variant of uncertain significance (VUS). For those unaffected patients, 58 (15%) had a positive result and 10 (3%) were found to have a VUS. The results from this study are useful in describing genetic testing outcomes in this high‐risk underserved community. Repeatedly, the literature reports that individuals from diverse or limited resource settings are less likely to access genetic testing. Continued research efforts should be devoted to promoting the access of genetic testing in the high‐risk, underserved community.