Larissa Nekhlyudov

Risk of Heart Failure in Breast Cancer Patients After Anthracycline and Trastuzumab Treatment: A Retrospective Cohort Study

Background Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM. Methods We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. Results Among 12 500 women (mean age = 60 years, range = 22–99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35). Conclusions Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.

Contentment With Quality of Life Among Breast Cancer Survivors With and Without Contralateral Prophylactic Mastectomy

PURPOSE To understand psychosocial outcomes after prophylactic removal of the contralateral breast in women with unilateral breast cancer. METHODS We mailed surveys to women with contralateral prophylactic mastectomy after breast cancer diagnosis between 1979 and 1999 at six health care delivery systems, and to a smaller random sample of women with breast cancer without the procedure. Measures were modeled on instruments developed to assess contentment with quality of life, body image, sexual satisfaction, breast cancer concern, depression, and health perception. We examined associations between quality of life and the other domains using logistic regression. RESULTS The response rate was 72.6%. Among 519 women who underwent contralateral prophylactic mastectomy, 86.5% were satisfied with their decision; 76.3% reported high contentment with quality of life compared with 75.4% of 61 women who did not undergo the procedure (P = .88). Among all case subjects, less contentment with quality of life was not associated with contralateral prophylactic mastectomy or demographic characteristics, but was associated with poor or fair general health perception (odds ratio [OR], 7.0; 95% CI, 3.4 to 14.1); possible depression (OR, 5.4; 95% CI, 3.1 to 9.2); dissatisfaction with appearance when dressed (OR, 3.5; 95% CI, 2.0 to 6.0); self-consciousness about appearance (OR, 2.0; 95% CI, 1.1 to 3.7); and avoiding thoughts about breast cancer (modest: OR, 2.2; 95% CI, 1.1 to 4.5; highest: OR, 1.7; 95% CI, 0.9 to 3.2). CONCLUSION Most women undergoing contralateral prophylactic mastectomy report satisfaction with their decision and experience psychosocial outcomes similar to breast cancer survivors without the procedure.

Positive, Negative, and Disparate—Women’s Differing Long‐Term Psychosocial Experiences of Bilateral or Contralateral Prophylactic Mastectomy

Abstract:  Because of recent studies showing strong prevention benefit and acceptable psychosocial outcomes, more women may be considering prophylactic mastectomy. A growing literature shows some positive psychosocial outcomes for women with bilateral prophylactic mastectomy, but less is known about women with contralateral prophylactic mastectomy. Several surveys have shown that a large majority of women with prophylactic mastectomy report satisfaction with their decisions to have the procedure when asked in a quantitative, closed‐ended format. We sought to explore the nuances of women’s satisfaction with the procedure using a qualitative, open‐ended format. We included open‐ended questions as part of a mailed survey on psychosocial outcomes of prophylactic mastectomy. The research team coded and analyzed these responses using qualitative methods. We used simple descriptive statistics to compare the demographics of the entire survey sample to those women who answered the open‐ended questions; the responses to the open‐ and closed‐ended satisfaction questions, and the responses of women with bilateral and contralateral prophylactic mastectomy. Seventy‐one percent of women with prophylactic mastectomy responded to the survey and 48% provided open‐ended responses about psychosocial outcomes. Women’s open‐ended responses regarding psychosocial outcomes could be coded into one of three general categories—positive, negative, and disparate. In the subgroup of women with both open‐and closed‐ended responses, over 70% of women providing negative and disparate comments to the open‐ended question simultaneously indicated satisfaction on a closed‐ended question. Negative and disparate open‐ended responses were twice as common among women with bilateral prophylactic mastectomy (52%) than women with contralateral prophylactic mastectomy (26%). These findings suggest that even among women who report general satisfaction with their decision to have prophylactic mastectomy via closed‐ended survey questions, lingering negative psychosocial outcomes can remain, particularly among women with bilateral prophylactic mastectomy. This dichotomy could be an important factor to discuss in counseling women considering the procedure.

A model-based estimate of cumulative excess mortality in survivors of childhood cancer.

BACKGROUND Although childhood cancer survival rates have dramatically increased, survivors face elevated risk for life-threatening late effects, including secondary cancer. OBJECTIVE To estimate the cumulative effect of disease- and treatment-related mortality risks on survivor life expectancy. DESIGN State-transition model to simulate the lifetime clinical course of childhood cancer survivors. SETTING Childhood Cancer Survivor Study. PATIENTS Five-year survivors of childhood cancer. MEASUREMENTS Probabilities of risk for death from the original cancer diagnosis, excess mortality from subsequent cancer and cardiac, pulmonary, external, and other complications, and background mortality (age-specific mortality rates for the general population) were estimated over the lifetime of survivors of childhood cancer. RESULTS For a cohort of 5-year survivors aged 15 years who received a diagnosis of cancer at age 10 years, the average lifetime probability was 0.10 for late-recurrence mortality; 0.15 for treatment-related subsequent cancer and death from cardiac, pulmonary, and external causes; and 0.05 for death from other excess risks. Life expectancy for the cohort of persons aged 15 years was 50.6 years, a loss of 10.4 years (17.1%) compared with the general population. Reduction in life expectancy varied by diagnosis, ranging from 4.0 years (6.0%) for kidney tumor survivors to more than 17.8 years (> or =28.0%) for brain and bone tumor survivors, and was sensitive to late-recurrence mortality risk and duration of excess mortality risk. LIMITATION Estimates are based on data for survivors who received treatment 20 to 40 years ago; patients who received treatment more recently may have more favorable outcomes. CONCLUSION Childhood cancer survivors face considerable mortality during adulthood, with excess risks reducing life expectancy by as much as 28%. Monitoring the health of current survivors and carefully evaluating therapies with known late toxicities in patients with newly diagnosed cancer are needed.

Rapid Increase in Breast Magnetic Resonance Imaging Use: Trends From 2000 to 2011

IMPORTANCE Breast magnetic resonance imaging (MRI) is highly sensitive for detecting breast cancer. Low specificity, cost, and little evidence regarding mortality benefits, however, limit recommendations for its use to high-risk women. How breast MRI is actually used in community settings is unknown. OBJECTIVE To describe breast MRI trends and indications in a community setting. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at a not-for-profit health plan and multispecialty group medical practice in New England of 10,518 women aged 20 years and older enrolled in the health plan for at least 1 year who had at least 1 breast MRI between January 1, 2000, and December 31, 2011. MAIN OUTCOMES AND MEASURES Breast MRI counts were obtained from claims data. Clinical indication (screening, diagnostic evaluation, staging or treatment, or surveillance) was determined using a prediction model developed from electronic medical records on a subset of participants. Breast cancer risk status was assessed using claims data and, for the subset, also through electronic medical record review. RESULTS; Breast MRI use increased more than 20-fold from 6.5 per 10,000 women in 2000 to 130.7 per 10,000 in 2009. Use then declined and stabilized to 104.8 per 10,000 by 2011. Screening and surveillance, rare indications in 2000, together accounted for 57.6% of MRI use by 2011; 30.1% had a claims-documented personal history and 51.7% a family history of breast cancer, whereas 3.5% of women had a documented genetic mutation. In the subset of women with electronic medical records who received screening or surveillance MRIs, only 21.0% had evidence of meeting American Cancer Society (ACS) criteria for breast MRI. Conversely, only 48.4% of women with documented deleterious genetic mutations received breast MRI screening. CONCLUSIONS AND RELEVANCE Breast MRI use increased steeply over 10 years and then stabilized, especially for screening and surveillance among women with family or personal history of breast cancer; most women receiving screening and surveillance breast MRIs lacked documented evidence of meeting ACS criteria, and many women with mutations were not screened. Efforts are needed to ensure that breast MRI use and documentation are focused on those women who will benefit most.

Quality of Life After Bilateral Prophylactic Mastectomy

BackgroundBilateral prophylactic mastectomy in women with increased breast cancer risk dramatically reduces breast cancer occurrence but little is known about psychosocial outcomes.MethodsTo examine long-term quality of life after bilateral prophylactic mastectomy, we mailed surveys to 195 women who had the procedure from 1979 to 1999 and to a random sample of 117 women at increased breast cancer risk who did not have the procedure. Measures were modeled on or drawn directly from validated instruments designed to assess quality of life, body image, sexuality, breast cancer concerns, depression, health perception, and demographic characteristics. We used logistic regression to examine associations between quality of life and other domains.ResultsThe response rate was 58%, with 106 women with and 62 women without prophylactic mastectomy returning complete surveys. Among women who underwent bilateral prophylactic mastectomy, 84% were satisfied with their decision to have the procedure; 61% reported high contentment with quality of life compared with an identical 61% of women who did not have the procedure (P = 1.0). Among all subjects, diminished contentment with quality of life was not associated with bilateral prophylactic mastectomy but with dissatisfaction with sex life (adjusted ratio [OR] = 2.5, 95% confidence interval [CI] = 1.0–6.2), possible depression (CES-D > 16, OR = 4.9, CI = 2.0–11.8), and poor or fair general health perception (OR = 8.3, 95% CI = 2.4–29.0).ConclusionsThe majority of women reported satisfaction with bilateral prophylactic mastectomy and experienced psychosocial outcomes similar to women with similarly elevated breast cancer risk who did not undergo prophylactic mastectomy. Bilateral prophylactic mastectomy appears to neither positively nor negatively impact long-term psychosocial outcomes.

Beliefs and expectations of women under 50 years old regarding screening mammography: a qualitative study.

OBJECTIVE: Because shared decision making has been recommended for screening mammography by women under age 50, we studied women’s decision-making process regarding the procedure. DESIGN: Qualitative research design using in-depth semi-structured interviews. PATIENTS: Sixteen white and African-American women aged 38 to 45 receiving care at a large New England medical practice. MEASUREMENTS AND MAIN RESULTS: We identified the following content areas in women’s decision-making process: intentions for screening, motivating factors to undergo screening, attitudes toward screening mammography, attitudes toward breast cancer, and preferences for information and shared decision making. In our sample, all women had or intended to have a screening mammogram before age 50. They were motivated by the awareness of the recommendation to begin screening at age 40, knowing others with breast cancer, and a sense of personal responsibility for their health. Participants feared breast cancer and thought the benefits of screening mammography far outweighed its risks. Women’s preferences for involvement in decision making varied from wanting full responsibility for screening decisions to deferring to their medical providers. All preferred the primary care provider to be the main source of information, yet the participants stated that their own providers played a limited role in educating them about the risks and benefits of screening and the mammography procedure itself. Most of their information was derived from the media. CONCLUSIONS: The women in this study demonstrated little ambivalence in their desire for mammography screening prior to age 50. They reported minimal communication with their medical providers about the risks and benefits of screening. Better information flow regarding mammography screening is necessary. Given the lack of uncertainty among women’s perceptions regarding screening mammography, shared decision making in this area may be difficult to achieve.

Providing Care for Cancer Survivors in Integrated Health Care Delivery Systems: Practices, Challenges, and Research Opportunities

PURPOSE Optimal approaches to cancer survivorship care are needed. This study sought to identify practices, barriers, and research opportunities in meeting the care needs of cancer survivors in integrated health care delivery systems. METHODS This study was conducted at 10 sites within the Cancer Research Network, a National Cancer Institute-funded consortium of integrated health care delivery systems providing care for nearly 11 million enrollees. We identified 48 clinical leaders, administrators, and providers in oncology, primary care, nursing administration, and specialty care. Forty (83%) completed semi-structured, audio-recorded, transcribed telephone interviews, which we analyzed using an immersion-crystallization approach. RESULTS Respondents were aware of the needs of cancer survivors and the difficulties they face in transitioning from treatment to follow-up care. Respondents from all sites reported that oncology and primary care are jointly responsible for the care of cancer survivors, often through the use of electronic medical records. Many respondents were not familiar with standardized survivorship care plans. Only two sites had formal cancer survivorship programs in place, and two were developing such programs. Respondents at sites with and without programs acknowledged existing gaps in evidence on the effectiveness of formal survivorship care and expressed a desire for additional research. CONCLUSION Our exploratory study suggests an awareness of cancer survivorship care in integrated health care delivery systems, although approaches to providing such care vary across systems. These settings may offer a unique opportunity to develop, test, and implement innovative models of care, which can be systematically evaluated to inform and enhance cancer survivorship care in diverse health care settings.

Clinical and pathologic features of ductal carcinoma in situ associated with the presence of flat epithelial atypia: an analysis of 543 patients

Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. No prior study has systematically evaluated the relationship between various clinico-pathologic features of ductal carcinoma in situ and the presence of coexistent flat epithelial atypia. An understanding of such relationships could provide insight into the connection between flat epithelial atypia and ductal carcinoma in situ. We reviewed slides from 543 ductal carcinoma in situ patients enrolled in a case–control study assessing epidemiologic and pathologic risk factors for local recurrence. We examined the association between the presence of flat epithelial atypia and various clinical factors, pathologic features of the ductal carcinoma in situ, and the presence of coexistent atypical ductal hyperplasia, lobular neoplasia, and non-atypical columnar cell lesions. In univariate analysis, the presence of flat epithelial atypia was significantly related to ductal carcinoma in situ nuclear grade (most common in low grade, least common in high grade; P<0.0001), architectural pattern (most common in micropapillary and cribriform, least common in comedo; P<0.0001), absence of comedo necrosis (P<0.001), absence of stromal desmoplasia (P=0.02) and absence of stromal inflammation (P=0.03). In multivariable analysis, features of ductal carcinoma in situ independently associated with flat epithelial atypia were micropapillary and cribriform patterns and absence of comedo necrosis. Additionally, flat epithelial atypia was significantly associated with the presence of atypical ductal hyperplasia, lobular neoplasia, and columnar cell lesions in both univariate and multivariable analyses. These observations provide support for a precursor–product relationship between flat epithelial atypia and ductal carcinoma in situ lesions that exhibit particular features such as micropapillary and cribriform patterns and absence of comedo necrosis.

Doc, should I see you or my oncologist?: a primary care perspective on opportunities and challenges in providing comprehensive care for cancer survivors.

As a primary care provider, my answer to the question raised in the title of this editorial is simple: a cancer survivor should see a primary care provider. Ask an oncologist or a cancer survivor, and the answers are likely to vary. I have heard my oncology colleagues say that they enjoy “social” visits from their cancer survivors, but at the same time, they are concerned about their full schedules, which do not allow them sufficient time to see newly diagnosed patients. I have heard patients with cancer and their family members question the need to see primary care providers and ask in bewilderment which specialists they should see for their organ-related complaints. Although I have had cancer survivors who have “forgotten” about their prior cancer diagnoses, I have 5-year survivors of early breast cancer who not only see me regularly, but also seek annual visits with their oncologists, radiation oncologists, surgical oncologists, and gynecologists. In light of the growing number of cancer survivors, many of whom are living longer, the article by Cheung et al addressing survivorship care in this issue of Journal of Clinical Oncology (JCO) is relevant and timely. Cheung et al surveyed 255 primary care providers, 123 oncologists, and 431 of their so-called cancer-free patients to compare expectations for cancer survivorship care. The survey asked patients to describe the degree of responsibility that their primary care providers or the oncologists should assume with respect to surveillance of their most recent cancer, screening for cancers other than their primary malignancy, general preventive health, and management of other comorbidities. The physician surveys—sent to the one primary care provider and one oncologist identified by each patient as the main physicians responsible for his or her care—asked physicians to describe their perceived roles in the same four areas. The study included 409 matched patient-oncologist pairs, 233 patient–primary care provider pairs, and 232 primary care provider–oncologist pairs. The study found that although patients expected both their oncologists and primary care providers to be involved in surveillance for cancer recurrence and other cancer screening, they expected the oncologists to be primarily responsible for cancer recurrence. Although most oncologists agreed with having a significant role in surveillance for cancer recurrence, about half expected to play a minimal role in screening for other cancers, and about one third expected to share this responsibility with the primary care providers. Most primary care providers expected to be responsible for both screening for other cancers and cancer recurrence, although about one third expected to share this role with the oncologists. Patients clearly preferred their primary care providers to have a major role in general preventive care and treatment of other comorbidities, and did not expect their oncologists to have a significant role in these aspects of care. For the most part, primary care providers and oncologists agreed with their patients. Oncologists and primary care providers agreed that the latter group should have a significant role in treating other medical problems (in fact, 84% of primary care providers expected to have full responsibility). Although oncologists were interested in sharing responsibility for general preventive care with primary care providers, primary care providers expected to have full or most of the responsibility for this aspect of care. The Cheung et al findings suggest that patients expect their oncologists, primary care providers, or both to be responsible for their care; that oncologists want to have a role in cancer-related care; and, not surprising to me, that my primary care colleagues expect to have a significant role in essentially all domains of cancer survivorship care. So where do we go from here? What is the role of primary care providers in cancer survivorship care? Whether patients have cancer, congestive heart failure, or diabetes, primary care providers are trained to provide comprehensive care to patients with complex medical conditions. Therefore, primary care providers should be best equipped to handle each of the four areas of cancer survivorship care outlined in the Cheung et al study. But are they? Great focus is placed on chronic diseases, such as congestive heart failure, diabetes, and end-stage renal disease, in general medical education and residency training. However, aside from the few exceptions likely to emerge, there are no curricula focusing on cancer survivorship. General medical training in cancer focuses on the acute phase and occurs mostly in inpatient settings (although there is some exposure to ambulatory care). In previous studies, although primary care providers expressed an interest in caring for cancer survivors, only about half reported being comfortable with having responsibility for surveillance of cancer recurrence. Caring for adult survivors of JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 27 NUMBER 15 MAY 2