Breast cancer survivors' satisfying marriages predict better psychological and physical health: A longitudinal comparison of satisfied, dissatisfied, and unmarried women.

OBJECTIVE: Breast cancer survivors who experience psychological and physical symptoms after treatment have an increased risk for comorbid disease development, reduced quality of life, and premature mortality. Identifying factors that reduce or exacerbate their symptoms may enhance their long-term health and physical functioning. This study examined how survivors' marital status and marital satisfaction-key health determinants-impacted their psychological and physical health trajectories to understand when, and for whom, marriage offers health benefits. METHODS: Breast cancer survivors (n = 209, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed questionnaires assessing their marital status and satisfaction when applicable, as well as their psychological (depressive symptoms, stress) and physical (fatigue, pain) health at each visit. RESULTS: Married women-both those in satisfying and dissatisfying marriages-experienced improvements in their depressive symptoms, stress, and fatigue from pretreatment to 6- and 18-month posttreatment. Unmarried (i.e., single, divorced/separated, or widowed) women's depressive symptoms, stress, fatigue, and pain did not change over time, instead remaining elevated 6 and 18 months after treatment ended. Women in satisfying marriages also had fewer psychological and physical symptoms after treatment than those who were unmarried or in dissatisfying marriages. CONCLUSIONS: Although marriage was associated with improved psychological and physical health, the gains were most notable when survivors' marriages were satisfying. Thus, the quality of survivors' marriages, rather than the marriage itself, provided the most benefits to their psychological and physical health.

Long-Term Efficacy of Lymph Node Reoperation for Persistent Papillary Thyroid Cancer: 13-Year Follow-Up.

BACKGROUND: Current recommendations for persistent or recurrent locoregional papillary thyroid cancer (PTC) include consideration of surgical resection versus active surveillance. The purpose of this study is to determine long-term outcomes after surgical resection of recurrent or persistent metastatic PTC in cervical lymph nodes after failure of initial surgery and radioactive iodine therapy using newer validated clinical outcomes measures. METHODS: Outcomes of 70 patients who underwent cervical lymphadenectomy (n = 110) from 1999 to 2013 for recurrent or persistent locoregional PTC metastases were reviewed. Measures included biochemical remission (BCR) based on Tg levels, American Thyroid Association classifications for response to treatment [biochemical incomplete response (BIR), structural incomplete response (SIR), indeterminate response (IR), and excellent response (ER)], need for reoperation, surgical complications, disease progression, and death. RESULTS: The median follow-up was 13.1 years, with only two additional reoperations since 2010, one of which had no metastasis on pathology with the other developing anaplastic thyroid cancer in background PTC. ER was achieved in 31 (44%) patients, all of whom remained in ER at time of last follow-up (median 14.1 years). There were no structural recurrences in patients with persistent BIR or IR after reoperation. Patients with SIR had stable disease, except for one who died due to anaplastic thyroid cancer. CONCLUSIONS: Patients who achieved ER after reoperation had no need for further treatment. Patients with persistent detectable Tg levels after reoperation rarely developed structural recurrence. ATA outcomes can be safely used to guide treatment decisions over a decade after reoperation for PTC.

Physical Activity After Breast Cancer Surgery: Does Depression Make Exercise Feel More Effortful than It Actually Is?

BACKGROUND: Prior to treatment, breast cancer patients are less physically fit compared to peers; during cancer treatment, their fitness typically declines. Depressive symptoms are associated with reduced activity up to 5 years post-treatment, but research has not identified mechanisms linking depression and lower activity. The current study assessed relationships among breast cancer patients' depression and perceived exertion during exercise as well as heart rate, an objective indicator of exertion. METHODS: Participants were 106 breast cancer patients, stages I-IIIA, who completed surgery but had not started adjuvant treatment. Heart rate and self-rated exertion, measured using the Borg Scale of Perceived Exertion, were assessed every 2 min during a graded exercise test. Depression was assessed using the CES-D and a structured clinical interview. RESULTS: Compared to women below the CES-D clinical cutoff, women with significant depressive symptoms reported steeper increases in exertion during the exercise test (p = .010) but had similar heart rates (p = .224) compared to women below the cutoff. Major depression history was unrelated to perceived exertion (ps > .224) and heart rate (ps > .200) during exercise. CONCLUSIONS: Women with currently elevated depressive symptoms experienced exercise as more difficult compared to women below the CES-D cutoff, but these self-perceptions did not reflect actual heart rate differences. Depression may make exercise feel more demanding, which could ultimately decrease patients' likelihood of engaging in regular exercise. Results support the use of depression screening tools following breast cancer surgery to identify and intervene on individuals at risk for decreased physical activity during survivorship.

NCCN Guidelines Insights: Breast Cancer, Version 3.2018.

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor-positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

Breast Cancer Screening and Diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Breast Cancer Screening and Diagnosis have been developed to facilitate clinical decision making. This manuscript discusses the diagnostic evaluation of individuals with suspected breast cancer due to either abnormal imaging and/or physical findings. For breast cancer screening recommendations, please see the full guidelines on NCCN.org.

Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology.

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

NCCN Guidelines Insights: Breast Cancer, Version 1.2017.

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors Versus Noncancer Controls: Evidence for Accelerated Aging?

Purpose The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group. Methods Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1ß). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group). Results There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group. Conclusion Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.

Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ.

OBJECTIVE: The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety. METHODS: Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments. RESULTS: The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay. CONCLUSIONS: Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.

Invasive Breast Cancer Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org.

NCCN Guidelines Insights Breast Cancer, Version 1.2016.

These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor-positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.

Processes of Care in Breast Reconstruction and the Long-Term Impact of a Comprehensive Breast Center.

BACKGROUND: Increased emphasis has been placed on process outcomes for breast cancer care, but limited data exists on these measures for breast reconstruction. These processes are likely to be impacted by increased centralization of care into comprehensive breast centers (CBC). Our study objectives were to define measures for processes of care in breast reconstruction and to determine the effect of a CBC on these measures. METHODS: A 5-year review was performed of patients who underwent mastectomy with or without reconstruction for a newly diagnosed breast cancer between 2010 and 2014, which spans from 1 year before to 4 years after introduction of our CBC. RESULTS: A total of 4179 patients were reviewed. The referral rate for immediate reconstruction increased from 40.0 to 70.8 % (p < .001), and the immediate reconstruction rate increased from 36.7 to 65.0 % (p < .001), both plateauing in the fourth study year. The interval between surgical oncology and plastic surgery consultation decreased (from 9.2 to 2.5 days; p < .001), and stabilized in the second study year. The interval between plastic surgery consultation and surgery decreased throughout the entire study period (from 37.6 to 20.8 days; p < .001), resulting in continued improvements in the interval between surgical oncology consultation and surgery (from 46.8 to 23.3 days, p < .001). CONCLUSIONS: In breast reconstruction, a CBC results in improvements in process outcomes, some of which are realized in the short-term and others in the long-term. The timeliness of treatment of patients who undergo immediate postmastectomy reconstruction can be similar to targets set for patients who undergo mastectomy alone.

Breast Cancer Version 2.2015.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This portion of the NCCN Guidelines discusses recommendations specific to the locoregional management of clinical stage I, II, and IIIA (T3N1M0) tumors.

Process outcomes in breast reconstruction and the impact of a comprehensive breast center.

BACKGROUND: Processes outcomes for breast reconstruction (related to access, efficiency, and sustainability) have not been well described. These processes are likely to be impacted by the centralization of breast cancer care into comprehensive breast centers. The authors' study objectives were to define measures for breast reconstruction processes of care and to determine a breast center's effect on these measures. METHODS: All patients evaluated for postmastectomy breast reconstruction between 2009 and 2013 (2 years before to 2 years after opening of the authors' breast center) were reviewed. Consultation, surgical, and financial data were compared between the two periods. RESULTS: A total of 614 (45.0 percent) and 750 patients (55.0 percent) were treated before and after, respectively, formation of the authors' breast center. Between the two periods, the internal referral rate for postmastectomy reconstruction increased from 27.1 percent to 46.0 percent (p<0.001). The delay between surgical oncology and plastic surgery consultation decreased from 10.5 days to 3.6 days (p<0.001), as did the delay between plastic surgery consultation and surgery for both autologous (from 45.1 days to 32.6 days; p=0.003) and implant-based reconstruction (from 34.9 days to 25.5 days; p=0.004). The immediate breast reconstruction rate increased from 40.1 percent to 52.7 percent (p<0.001), including autologous reconstruction (from 13.1 percent to 20.8 percent; p<0.001). CONCLUSIONS: In breast reconstruction, a comprehensive breast center improves processes of care. The authors describe their strategy for integration of reconstructive surgery into a breast center.

Attachment anxiety is related to Epstein-Barr virus latency.

Attachment theory provides a framework for understanding individual differences in chronic interpersonal stress. Attachment anxiety, a type of relationship insecurity characterized by worry about rejection and abandonment, is a chronic interpersonal stressor. Stress impacts cellular immunity, including herpesvirus reactivation. We investigated whether attachment anxiety was related to the expression of a latent herpesvirus, Epstein-Barr virus (EBV), when individuals were being tested for breast or colon cancer and approximately 1 year later. Participants (N=183) completed a standard attachment questionnaire and provided blood to assess EBV viral capsid antigen (VCA) IgG antibody titers. Individuals with more attachment anxiety had higher EBV VCA IgG antibody titers than those with less attachment anxiety. The strength of the association between attachment anxiety and antibody titers was the same at both assessments. This study is the first to show an association between latent herpesvirus reactivation and attachment anxiety. Because elevated herpesvirus antibody titers reflect poorer cellular immune system control over the latent virus, these data suggest that high attachment anxiety is associated with cellular immune dysregulation.

Cognitive problems among breast cancer survivors: loneliness enhances risk.

BACKGROUND: Cancer survivors often experience cognitive difficulties after treatment completion. Although chemotherapy enhances risk for cognitive problems, it is likely only one piece of a complex puzzle that explains survivors' cognitive functioning. Loneliness may be one psychosocial risk factor. The current studies included both subjective and objective cognitive measures and tested whether lonelier breast cancer survivors would have more concentration and memory complaints and experience more concentration difficulties than their less lonely counterparts. METHODS: The relationship between loneliness and cognitive function was tested among three samples of breast cancer survivors. Study 1 was a sample of breast cancer survivors (n = 200) who reported their concentration and memory problems. Study 2a was a sample of breast cancer survivors (n = 185) and noncancer controls (n = 93) who reported their concentration and memory problems. Study 2b was a subsample of Study 2a breast cancer survivors (n = 22) and noncancer controls (n = 21) who completed a standardized neuropsychological test assessing concentration. RESULTS: Studies 1 and 2a revealed that lonelier women reported more concentration and memory problems than less lonely women. Study 2b utilized a standardized neuropsychological continuous performance test and demonstrated that lonelier women experienced more concentration problems than their less lonely counterparts. CONCLUSIONS: These studies demonstrated that loneliness is linked to concentration and memory complaints and the experience of concentration problems among breast cancer survivors. The results were also highly consistent across three samples of breast cancer survivors. These data suggest that loneliness may be a risk factor for cognitive difficulties among cancer survivors.

Breast cancer version 3.2014.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The NCCN Guidelines specific to management of large clinical stage II and III tumors are discussed in this article. These guidelines are the work of the members of the NCCN Breast Cancer Panel. Expert medical clinical judgment is required to apply these guidelines in the context of an individual patient to provide optimal care. Although not stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer.

Social support predicts inflammation, pain, and depressive symptoms: longitudinal relationships among breast cancer survivors.

OBJECTIVE: Pain and depressive symptoms are commonly experienced by cancer survivors. Lower social support is linked to a variety of negative mental and physical health outcomes among survivors. Immune dysregulation may be one mechanism linking low social support to the development of pain and depressive symptoms over time. Accordingly, the goal of the present study was to examine the relationships among survivors' social support, pain, depressive symptoms, and inflammation. METHODS: Breast cancer survivors (N=164, stages 0-IIIA) completed two study visits, one before any cancer treatment and the other 6 months after the completion of surgery, radiation, or chemotherapy, whichever came last. Women completed self-report questionnaires assessing social support, pain, and depressive symptoms, and provided a blood sample at both visits. RESULTS: Survivors with lower social support prior to treatment experienced higher levels of pain and depressive symptoms over time than their more socially supported counterparts. Furthermore, women with lower pretreatment social support had higher levels of IL-6 over time, and these elevations in IL-6 predicted marginally larger increases in depressive symptoms. CONCLUSIONS: The results of this study suggest that social support at the time of diagnosis predicts the post-treatment development of pain, depressive symptoms, and inflammation. Consequently, early interventions targeting survivors' social networks could improve quality of life during survivorship.

Pain, depression, and fatigue: loneliness as a longitudinal risk factor.

OBJECTIVE: Pain, depression, and fatigue function as a symptom cluster and thus may share common risk factors. Interpersonal relationships clearly influence health, suggesting that loneliness may promote the development of the pain, depression, and fatigue symptom cluster. We hypothesized that loneliness would be related to concurrent symptom cluster levels and increases in symptom cluster levels over time. METHOD: We utilized two observational studies with distinct longitudinal samples. Study 1 was a sample of cancer survivors and benign controls (N = 115) assessed annually for 2 years. Study 2 was a sample of older adults caring for a spouse with dementia (caregivers) and non-caregiver controls (N = 229) assessed annually for 4 years. Participants completed annual measures assessing loneliness, pain, depression, and fatigue. RESULTS: Across both samples, lonelier participants experienced more concurrent pain, depression, and fatigue and larger increases in symptom cluster levels from one year to the next than less lonely participants. Sleep quality did not mediate the results in either study. All analyses were adjusted for relevant demographic and health variables. CONCLUSIONS: Two longitudinal studies with different populations demonstrated that loneliness was a risk factor for the development of the pain, depression, and fatigue symptom cluster over time. The current research helps identify people most at risk for pain, depression, and fatigue, and lays the groundwork for research about their diagnosis and treatment. These data also highlight the health risks of loneliness; pain, depression, and fatigue often accompany serious illness and place people at risk for poor health and mortality.

Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial.

BACKGROUND: We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment, and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients. METHODS: For this open-label, randomised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer. Each received four cycles of standard doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel (80 mg/m(2)) intravenously on days 1, 8, and 15, every 4 weeks. Concurrently with weekly paclitaxel, patients received either trastuzumab (4 mg/kg load, then 2 mg/kg intravenously) weekly until surgery, lapatinib (1250 mg orally) daily until surgery, or weekly trastuzumab plus lapatinib (750 mg orally) daily until surgery. After surgery, all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy. Randomisation (ratio 1:1:1) was done centrally with stratification by clinical tumour size, clinical nodal status, hormone-receptor status, and age. The primary endpoint was the pathological complete response in the breast, and analysis was performed on an intention-to-treat population. FINDINGS: Patient accrual started on July 16, 2007, and was completed on June 30, 2011; 529 women were enrolled in the trial. 519 patients had their pathological response determined. Breast pathological complete response was noted in 93 (52·5%, 95% CI 44·9-59·5) of 177 patients in the trastuzumab group, 91 (53·2%, 45·4-60·3) of 171 patients in the lapatinib group (p=0·9852); and 106 (62·0%, 54·3-68·8) of 171 patients in the combination group (p=0·095). The most common grade 3 and 4 toxic effects were neutropenia (29 [16%] patients in the trastuzumab group [grade 4 in five patients (3%), 28 [16%] in the lapatinib group [grade 4 in eight patients (5%)], and 29 [17%] in the combination group [grade 4 in nine patients (5%)]) and grade 3 diarrhoea (four [2%] patients in the trastuzumab group, 35 [20%] in the lapatinib group, and 46 [27%] in the combination group; p<0·0001). Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven (4%) patients in the trastuzumab group, seven (4%) in the lapatinib group, and one (<1%) in the combination group; p=0·185). INTERPRETATION: Substitution of lapatinib for trastuzumab in combination with chemotherapy resulted in similar high percentages of pathological complete response. Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy; these findings are consistent with results from other studies. Trials are being undertaken to further assess these findings in the adjuvant setting.