Jennifer R. Klemp

Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

PURPOSE Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. PATIENTS AND METHODS Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. RESULTS Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. CONCLUSION Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives.

Breast cancer and fertility preservation.

OBJECTIVE To review the benefits of adjuvant systemic therapy given to women with breast cancer of reproductive age, its effects on fertility, and options for fertility preservation. DESIGN Publications relevant to fertility preservation and breast cancer were identified through a PubMed database search. CONCLUSION(S) Most women who develop invasive breast cancer under age 40 will be advised to undergo adjuvant chemotherapy with or without extended antihormonal therapy to reduce the risk of recurrence and death from breast cancer. Adjuvant chemotherapy particularly with alkylating agents such as cyclophosphamide is gonadotoxic and markedly accelerates the rate of age-related ovarian follicle loss. Although loss of fertility is an important issue for young cancer survivors, there is often little discussion about fertility preservation before initiation of adjuvant therapy. Greater familiarity with prognosis and effects of different types of adjuvant therapy on the part of infertility specialists and fertility preservation options such cryopreservation of embryos, oocytes, and ovarian tissue on the part of oncologists would facilitate these discussions. Establishment of rapid fertility consultation links within cancer survivorship programs can help ensure that every young woman who is likely to undergo gonadotoxic cancer treatment is counseled about the effects of therapy and options available to her to increase the likelihood of childbearing after cancer treatment.

Breast cancer risk assessment and prevention: a framework for shared decision-making consultations.

Abstract:  Options for breast cancer prevention, used in combination with screening and surveillance, include lifestyle modifications, chemoprevention with tamoxifen, and prophylactic surgery. Preventive health decisions are often preference driven: patients typically must choose whether to initiate effective treatments that hold the possibility of side effects that can negatively impact quality of life. This situation demands that patients be well informed and have a full understanding of the risks associated with each option. Investigators have developed a comprehensive decision‐making framework designed to support breast cancer prevention consultations within a shared decision‐making setting. The framework integrates predictive information from current risk models within the context of a womans general health to appropriately frame breast cancer risk management consultations and outlines the application of available treatments and emerging biomarker information to individual patient decisions. Using an evidence‐based approach, specialized risk‐benefit projections can be provided in the clinical setting. A more comprehensive individualized risk profile allows for tailored medical management plans and can better prepare patients to make informed decisions. The framework is intended to encourage a shared decision‐making approach to prevention consultations, a method for researchers to increase accrual to trials, and to more quickly incorporate new findings into the routine of practice.

Understanding the Functional Late Effects and Informational Needs of Adult Survivors of Childhood Cancer

PURPOSE/OBJECTIVES To report functional (physical and cognitive) late effects, experiences, and information needs of adult survivors of childhood cancer. DESIGN Descriptive, mixed methods survey. SETTING Two pediatric oncology programs in the Midwest. SAMPLE Convenience sample of 272 young adult survivors. METHODS Voluntary survey completion by young adult survivors regarding late effects, experiences, and educational needs to develop appropriate comprehensive care programs for care provision before, during, and after transition to adult care. Survey domains were identified from existing survivorship literature and focused on all aspects of survivorship; however, this article focuses on results specific to the functional domain. MAIN RESEARCH VARIABLES Functional late effects, experiences, information needs, age, gender, and treatment intensity of young adult survivors of childhood cancer. FINDINGS Response rate was 48%. Functional late effects, perceptions, and information needs all correlated with intensity of treatment (those survivors most heavily treated experienced the most symptoms). Survivors wanted more information about late effects and how to deal with them. Women wanted more information about fertility-related topics, and participants who received more intense treatment generally wanted more information. Brain tumor survivors perceived greater cognitive difficulties, cognitive late effects, fatigue, and financial difficulties. CONCLUSIONS Survivors experience myriad physical late effects and require ongoing access to information as needs change over time. IMPLICATIONS FOR NURSING Identifying new and innovative ways to reach survivors and better meet needs is important for care, research, and program development. KNOWLEDGE TRANSLATION The findings of the research underscore the importance of continuous learning opportunities for adult survivors of childhood cancer. The findings also highlight the need for healthcare teams to better understand the current and long-term needs of this population. In addition to traditional communication approaches, technologies such as social media and telemedicine can provide innovative ways to deliver patient-centered care.

Oncology Nurses' Perspectives on the State of Cancer Survivorship Care: Current Practice and Barriers to Implementation

PURPOSE/OBJECTIVES to describe current survivorship care from the perspectives of oncology nurses. DESIGN descriptive. SETTING e-mail invitation to Web-based survey. SAMPLE 399 Oncology Nursing Society members providing care for patients initially treated more than one year previously. METHODS an online survey was used to evaluate current aspects of survivorship care. MAIN RESEARCH VARIABLES practice settings, services provided, and barriers to delivering survivorship care. FINDINGS few nurses (27%) worked in settings with a formal survivorship program. Several program components were provided significantly more often in outpatient settings, pediatric facilities, and workplaces with a formal survivorship program. At the transition from acute to follow-up care, the survivorship nursing care provided most often was scheduling for ongoing monitoring (71%) and the least likely was assistance for employment or legal issues (16%). The greatest barriers to providing survivorship care were lack of time and funding (46%). Among nurses new to oncology (fewer than five years), 49% indicated they lacked sufficient knowledge compared to 36% of nurses with more than five years of oncology experience. CONCLUSIONS findings describe current aspects of survivorship care across practice settings. Nurses reported that the greatest barriers are lack of time, funding, and lack of knowledge about survivorship issues. IMPLICATIONS FOR NURSING a need exists for education to enhance knowledge and skills of nurses who will provide survivorship care. Research is warranted to develop empirically supported guidelines and care-delivery models that address the barriers to providing survivorship services.

Reduction in Ki-67 in Benign Breast Tissue of High-Risk Women with the Lignan Secoisolariciresinol Diglycoside

Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a >3-fold increase in 5-year risk, and baseline Ki-67 of ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG (50 mg/d) was given for 12 months, followed by repeat RPFNA. The primary end point was change in Ki-67. Secondary end points included change in cytomorphology, mammographic breast density, serum bioavailable estradiol and testosterone insulin-like growth factor-I and IGF-binding protein-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ∼9-fold, and total lignans increased 16-fold. Thirty-six (80%) of the 45 evaluable subjects showed a decrease in Ki-67, from a median of 4% (range, 2-16.8%) to 2% (range, 0-15.2%; P < 0.001, Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (P = 0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG versus placebo in premenopausal women. Cancer Prev Res; 3(10); 1342–50. ©2010 AACR.

Improving Cancer Survivorship Care: Oncology Nurses’ Educational Needs and Preferred Methods of Learning

Oncology nurses are essential in all phases of cancer care; however, their role in survivorship care is unclear. To better understand the self-reported knowledge and educational needs on topics of survivorship care and oncology nurses’ learning preferences, an online survey was conducted. Respondents self-reported knowledge level for 31 care topics, identified areas of most interest, topics needed to assist patients and address patient questions, and reported participation in continuing education and preferred learning methods. Knowledge was rated highest for topics of fatigue, anxiety, and fear of recurrence and lowest for issues related to finance, employment, and insurance. Nurses were most interested in late and long-term physical effects of cancer or treatment, managing emotional issues, cancer screening and surveillance, and complementary and alternative therapies. Study findings suggest that online learning methods would be feasible and well accepted by nurses to meet continuing education needs related to cancer survivorship.

Failure of high risk women to produce nipple aspirate fluid does not exclude detection of cytologic atypia in random periareolar fine needle aspiration specimens

AbstractIntroduction. Evidence of hyperplasia with atypia found both on random periareolar fine needle aspiration (RPFNA) and in nipple aspirate fluid (NAF) fluid are associated with an increased risk for breast cancer. Aim. In this study, we report the correlation of NAF production with cytological assessment of ductal cells obtained by RPFNA. Methods. 113 women at high risk for development of breast cancer attending the Breast Cancer Prevention Clinic at the University of Kansas Medical Center underwent a single NAF collection attempt and RPFNA. Results. NAF was successfully collected in 51% of women. There was no significant difference in age, 5-year Gail risk assessment, menopausal status, hormone use, family history of breast cancer, history of prior atypical hyperplasia/LCIS or history of contralateral DCIS/invasive breast cancer between women who produced NAF and those that did not. The only significant difference between the two groups was in history of prior lactation (p= 0.018). Twenty-seven of the 113 subjects were found to have hyperplasia with atypia by RPFNA was 31% in women who produced NAF versus 16% in those who did not (p= 0.07). Conclusion. Although prevalence of RPFNA atypia was numerically higher in NAF producers than non-producers the difference did not reach statistical significance. Failure to produce NAF does not exclude the presence of hyperplasia with atypia by random periareolar fine needle aspiration.

Weight control needs and experiences among rural breast cancer survivors

Objective: Rural women are understudied in research on weight control among breast cancer survivors despite having higher obesity rates than their urban counterparts placing them at higher risk for recurrence. The purpose of this survey study was to describe weight status and methods used for weight control in rural breast cancer survivors and to examine psychosocial factors in this population associated with weight change since breast cancer diagnosis.

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.