Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations.

PURPOSE: We evaluated the efficacy and safety of poly-(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 inhibitor veliparib and temozolomide in metastatic breast cancer patients with and without germline BRCA1/2 mutations. METHODS: In this single-arm phase II trial, patients with metastatic breast cancer received veliparib 30 to 40 mg twice daily on days 1 to 7 with concurrent temozolomide 150 mg/m2 on days 1 to 5 of a 28-day cycle. The primary cohort was unselected for BRCA mutation status, and an expansion cohort enrolled only BRCA1/2 carriers. The primary endpoint was objective response rate (ORR) in each cohort. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and evaluation of safety and tolerability. RESULTS: In the primary cohort of 41 unselected patients, which included 9 BRCA mutation carriers, the ORR was 10% and clinical benefit rate at 4 months (CBR) was 27%. In the expansion cohort of 21 BRCA1/2 carriers, the ORR was 14% and CBR was 43%. Among all 30 BRCA1/2 carriers, the ORR was 23% versus 0% among non-carriers. In the subset of BRCA1/2 carriers, the ORR was 32% among platinum-naïve patients versus 9% among platinum-exposed patients. The median PFS was 3.3 months among BRCA1/2 carriers compared to 1.8 months among non-carriers (HR: 0.48, p = 0.006). A longer median PFS of 6.2 months was observed among BRCA1/2 carriers who had no prior platinum therapy. The most common grade 3 and 4 toxicities were thrombocytopenia (32%) and neutropenia (21%) that generally improved with dose modifications. CONCLUSION: Veliparib and temozolomide demonstrated clinical activity in platinum-naïve BRCA-associated metastatic breast cancer with manageable toxicity at doses of veliparib well below the single-agent active dose. Although the study did not meet its primary endpoint in unselected nor BRCA-associated breast cancer, this regimen was further evaluated in the BROCADE 2 study. TRIAL REGISTRATION: NCT01009788 (ClinicalTrials.gov), November 9, 2009.

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

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 God's 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.

A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen.

Tamoxifen significantly reduces tumor recurrence in certain patients with early-stage estrogen receptor-positive breast cancer, but markers predictive of treatment failure have not been identified. Here, we generated gene expression profiles of hormone receptor-positive primary breast cancers in a set of 60 patients treated with adjuvant tamoxifen monotherapy. An expression signature predictive of disease-free survival was reduced to a two-gene ratio, HOXB13 versus IL17BR, which outperformed existing biomarkers. Ectopic expression of HOXB13 in MCF10A breast epithelial cells enhances motility and invasion in vitro, and its expression is increased in both preinvasive and invasive primary breast cancer. The HOXB13:IL17BR expression ratio may be useful for identifying patients appropriate for alternative therapeutic regimens in early-stage breast cancer.

Cutaneous Metastases: A Case Study on Clinical Care for Patients.

Cutaneous metastases (CMs) signal the spread of a primary tumor to the skin and dermis, particularly in patients with melanoma or with breast, lung, or gastrointestinal cancers. Although these lesions may present as superficial and painless, some CMs may lead to ulceration, drainage, and discomfort, causing distress to patients. Oncology nurses require knowledge about the clinical presentation of CMs, including incidence, pathophysiology, diagnostic evaluation, and complex symptomatology, as well as standard treatment and care for patients. In addition, nurses can provide psychosocial interventions to assist patients experiencing distress from CM lesions.

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.

Applying a conceptual model for examining health-related quality of life in long-term breast cancer survivors: CALGB study 79804.

OBJECTIVES: The Survivor's 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. METHODS: A total of 245 survivors (78% of those invited) who were 9.4-16.5 years post-diagnosis completed surveys that inquired about current HRQL, economic, spiritual, physical and psychosocial concerns, and health-oriented behaviors (e.g. smoking, exercise, and supplement use). A regression model was developed to examine factors related to global HRQL across all domains. RESULTS: The regression model revealed that decreased energy levels (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.03, 1.07), having heart disease (OR=5.01, 95% CI: 1.39, 18.1), having two or more co-morbidities (OR=2.39, 95% CI: 1.10, 5.19), and lower social support (OR=1.03, 95% CI: 1.02, 1.05) were associated with lower global HRQL. Factors related to psychological, spiritual, and economic domains were not predictive of global HRQL. Regarding lifestyle changes, some women reported engaging in health-oriented behaviors since their cancer diagnosis, such as improving eating habits (54%), increasing exercise (32%), and reducing/quitting smoking (20%). The most prevalent problems reported by women at follow-up were menopausal symptoms (64%), such as hot flashes and vaginal dryness, osteoporosis (25%), and lymphedema (23%). CONCLUSION: Suggestions are provided to target interventions, such as provider-based strategies, in order to improve HRQL in long-term breast cancer survivors.

Research Biopsies: An Integrative Review of the Experiences of Patients With Cancer.

BACKGROUND: Research biopsies (RBs) are essential to understanding tumor biology and mechanisms of resistance and to advancing precision medicine. However, RBs have associated risks and may not benefit the patient. OBJECTIVES: The purpose of this integrative review is to summarize and synthesize the current literature on the experience, attitudes, and understanding of patients with cancer related to RBs. METHODS: Articles from January 2010 to February 2017 were retrieved via a search of MEDLINE®. Articles included reported on the willingness, perceptions, understanding, attitudes, and/or experience of patients with cancer related to RBs. FINDINGS: Nine of 216 identified studies were selected. Studies exploring patient willingness to undergo RBs (n = 6) identified RBs as a potential barrier to clinical trial participation. Studies exploring patient understanding and informed consent (n = 3) revealed variable patient knowledge of the risks and benefits of RBs.

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.

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.

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.

The Experience of Initiating Oral Adjuvant Treatment for Estrogen Receptor-Positive Breast Cancer.

PURPOSE/OBJECTIVES: To describe the experience of women with estrogen receptor-positive breast cancer who are initiating oral adjuvant therapy and to determine what they describe as facilitating and/or hindering this experience. 
. RESEARCH APPROACH: Qualitative inquiry. 
. SETTING: Massachusetts General Hospital Cancer Center in Boston. 
. PARTICIPANTS: 14 women aged 48-81 years. 
. METHODOLOGIC APPROACH: Qualitative, descriptive study using content analysis.
. FINDINGS: Five themes were identified. CONCLUSIONS: Each participant who was initiating oral adjuvant treatment described many unmet needs. Women who were caregivers, were older aged, had several chronic illnesses, and were on several medications reported more difficulty transitioning to oral adjuvant therapy. 
. INTERPRETATION: This study suggests that nurses need to collaborate with other members of the healthcare team to assess the needs of and provide comprehensive care to women initiating oral adjuvant therapy. This is particularly true for women who are older aged, self-reported caregivers, and on several medications, and who have chronic comorbid conditions.

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.

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: Women's 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 women's 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.

"I feel like I am 100 years old!" managing arthralgias from aromatase inhibitors.

Aromatase inhibitors (AIs) are recommended for the treatment of estrogen-sensitive breast cancer in postmenopausal women and provide a superior risk reduction compared to five years of tamoxifen alone. Arthralgias, a common side effect of AIs, may adversely affect quality of life, treatment adherence, and persistence. Early discontinuation of AIs may result in an inadequate clinical response. Over-the-counter analgesics, exercise, and drug holidays are common strategies used to manage arthralgias, however few interventions are evidence-based. Patients experiencing arthralgias may experience distress and, therefore would benefit from ongoing nursing support. When caring for patients with arthralgias, nurses should assess for potential modifiable risk factors, recommend lifestyle changes and/or pharmacologic interventions, and offer ongoing education and follow-up.

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.