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This study explored the perspectives and experiences of breast cancer patients and medical oncologists with regards to participation in a lifestyle intervention at a tertiary cancer treatment center. A thematic approach was used to understand the context within which a lifestyle intervention was recommended and experienced, to inform future lifestyle programming and promote uptake. Twelve women with breast cancer receiving adjuvant chemotherapy and eight medical oncologists completed interviews. Findings suggest receiving a prescription for a lifestyle intervention from a trusted health professional was influential to women with breast cancer. The intervention offered physical, psychological, emotional, social, and informational benefits to the women and oncologists perceived both physiological and relational benefit to prescribing the intervention. Challenges focused on program access and tailored interventions. Lifestyle prescriptions are perceived by women with breast cancer to have numerous benefits and may promote lifestyle interventions and build rapport between oncologists and women. Oncology healthcare professionals play a pivotal role in motivating women's participation in lifestyle interventions during breast cancer treatment. Maintenance programs that transition patients into community settings and provide on-going information and follow-up are needed.

Background: Overwhelming randomized controlled trial evidence demonstrates that exercise has positive health impacts during and after treatment for breast cancer. Yet, evidence generated by studies in which exercise programs are delivered outside a tightly controlled randomized trial setting is limited. The purpose of this study was to assess the effectiveness of an evidence-based exercise program with real-world implementation on physical fitness and quality of life (QoL)., Patients and Methods: Oncologists referred women with early-stage breast cancer who were scheduled to receive adjuvant chemotherapy. The program consisted of supervised aerobic and resistance exercise of moderate to vigorous intensity 3 times per week until the end of treatment (chemotherapy ± radiotherapy), then twice per week for 10 weeks, followed by once per week for 10 weeks. Health-related physical fitness and QoL were assessed at baseline, end of treatment, end of program, and 1-year follow-up., Results: A total of 73 women were enrolled. Estimated peak VO2 (VO2peak), QoL, and body weight were maintained between baseline and end of treatment, whereas muscular strength improved (P<.01). By the end of the program, VO2peak, heart rate recovery, waist circumference, and some aspects of QoL were improved (all P<.01) relative to baseline. One year later, VO2peak, QoL, and waist circumference were maintained relative to end of program, whereas the improvements in strength and heart rate recovery had dissipated (all P<.01)., Conclusions: Evidence-based exercise programming delivered with real-world implementation maintained VO2peak, strength, and QoL during adjuvant treatment and improved these measures after treatment completion among women with breast cancer. Continued guidance and support may be required for long-term maintenance of strength improvements in this population.

Purpose: For breast cancer (BrCa) survivors, premature menopause can result from conventional cancer treatment. Due to limited treatment options, survivors often turn to complementary therapies (CTs), but struggle to make informed decisions. In this study, we identified BrCa survivors' CT and general information and decision-making needs related to menopausal symptoms., Methods: The needs assessment was informed by interpretive descriptive methodology. Focus groups with survivors (n = 22) and interviews with conventional (n = 12) and CT (n = 5) healthcare professionals (HCPs) were conducted at two Canadian urban cancer centers. Thematic, inductive analysis was conducted on the data., Results: Menopausal symptoms have significant negative impact on BrCa survivors. Close to 70 % of the sample were currently using CTs, including mind-body therapies (45.5 %), natural health products (NHPs) and dietary therapies (31.8 %), and lifestyle interventions (36.4 %). However, BrCa survivors reported inadequate access to information on the safety and efficacy of CT options. Survivors also struggled in their efforts to discuss CT with HCPs, who had limited time and information to support women in their CT decisions. Concise and credible information about CTs was required by BrCa survivors to support them in making informed and safe decisions about using CTs for menopausal symptom management., Conclusions: High quality research is needed on the efficacy and safety of CTs in managing menopausal symptoms following BrCa treatment. Decision support strategies, such as patient decision aids (DAs), may help synthesize and translate evidence on CTs and promote shared decision-making between BrCa survivors and HCPs about the role of CTs in coping with menopause following cancer treatment.

Purpose: The purpose of this study is to qualitatively describe the experiences of breast cancer survivors who took part in a successful 24-week lifestyle intervention aimed at weight loss. The aim was to inform future study designs and lifestyle interventions., Methods: Nine women who completed the lifestyle intervention took part in either a focus group or telephone interviews with trained facilitators who were not involved in the delivery of the intervention. Interviews were transcribed verbatim and thematic analysis was conducted., Results: Women appreciated the group-based nature of the program, the presence of other breast cancer survivors, and the safe and supportive environment provided by program leaders. The intervention supported women in reframing their dietary habits, and the exercise component had unexpected benefits on their psychological wellbeing. The logistics of fitting the intervention into busy work and family schedules was a challenge experienced by most women. Recommendations for future programming included offering the intervention to all survivors immediately following adjuvant treatment, integrating participants' social networks into the program and including a maintenance phase for sustainability of healthy behaviors., Conclusion: This qualitative study provides insight into breast cancer survivors' experiences in a group-based lifestyle intervention and offers suggestions for the development of future lifestyle programming in cancer care.

Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy. Patients with rising prostate-specific antigen (PSA) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo. Tolerability of the soy beverage and compliance were assessed. PSA doubling times before and after the consumption of soy were compared. Thirty-four subjects were enrolled; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption. All remaining 29 subjects were included in the analysis. Mean consumption of the assigned soy beverage was 93%. Mild gastrointestinal upset (38%) not affecting soy consumption was the commonest side effect. PSA showed a declining trend in 4 patients (13.8%), and there was a > 100% prolongation of PSA doubling time in 8 patients (27.6%). However, PSA doubling time also showed a 50% or more shortening in 5 patients (17.2%). In our cohort of North American subjects, 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41% of subjects. Confirmatory studies are warranted.

High levels of insulin have been associated with increased risk of breast cancer, and poorer survival after diagnosis. Data and sera were collected from 603 breast cancer patients, including information on diet and physical activity, medical history, family history, demographic, and reproductive risk factors. These data were analyzed to test the hypothesis that excess insulin and related factors are directly related to mortality after a diagnosis of breast cancer. The cohort was recruited from breast cancer patients treated at the British Columbia Cancer Agency between July 1991 and December 1992. Questionnaire and medical record data were collected at enrollment and outcomes were ascertained by linkage to the BC Cancer Registry after 10 years of follow-up. The primary outcome of interest was breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using Cox proportional hazards regression models to relate risk factors to outcomes, controlling for potential confounders, such as age and stage at diagnosis. Data for biological variables were analyzed as a nested case-control study due to limited serum volumes, with at least one survivor from the same cohort as a control for each breast cancer death, matched on stage and length of follow-up. High levels of insulin were associated with poorer survival for postmenopausal women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest to lowest tertile, P trend = 0.10], while high dietary fat intake was associated with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3-18.1, comparing highest to lowest quartile). Higher dietary protein intake was associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2-0.8, comparing highest to lowest quartile).

High insulin levels have been associated with increased risk of breast cancer and poorer survival after a breast cancer diagnosis. Waist-to-hip ratio (WHR) is a marker for insulin resistance and hyperinsulinemia. In this study, the authors tested the hypothesis that elevated WHR is directly related to breast cancer mortality. For identification of modifiable factors affecting survival, data were collected on 603 patients with incident breast cancer who visited the Vancouver Cancer Centre of the British Columbia Cancer Agency (Vancouver, British Columbia, Canada) in 1991-1992, including body measurements and information on demographic, medical, reproductive, and dietary factors. These patients were followed for up to 10 years. Cox proportional hazards regression models were used to relate the variables to breast cancer mortality (n = 112). After adjustment for age, body mass index, family history, estrogen receptor (ER) status, tumor stage at diagnosis, and systemic treatment (chemotherapy or tamoxifen), WHR was directly related to breast cancer mortality in postmenopausal women (for highest quartile vs. lowest, relative risk = 3.3, 95% confidence interval: 1.1, 10.4) but not in premenopausal women (relative risk = 1.2, 95% confidence interval: 0.4, 3.4). Stratification according to ER status showed that the increased mortality was restricted to ER-positive postmenopausal women. Elevated WHR was confirmed as a predictor of breast cancer mortality, with menopausal status and ER status at diagnosis found to be important modifiers of that relation.

Regulation of transcriptional responses in growth-arrested human cells under conditions that promote potentially lethal damage repair after ionizing radiation (IR) is poorly understood. Sp1/retinoblastoma control protein (RCP) DNA binding increased within 30 min and peaked at 2-4 h after IR (450-600 cGy) in confluent radioresistant human malignant melanoma (U1-Mel) cells. Increased phosphorylation of Sp1 directly corresponded to Sp1/RCP binding and immediate-early gene induction, whereas pRb remained hypophosphorylated. Transfection of U1-Mel cells with the human papillomavirus E7 gene abrogated Sp1/RCP induction and G(0)/G(1) cell cycle checkpoint arrest responses, increased apoptosis and radiosensitivity, and augmented genetic instability (i.e., increased polyploidy cells) after IR. Increased NF-kappaB DNA binding in U1-Mel cells after IR treatment lasted much longer (i.e., >20 h). U1-Mel cells overexpressing dominant-negative IkappaBalpha S32/36A mutant protein were significantly more resistant to IR exposure and retained both G(2)/M and G(0)/G(1) cell cycle checkpoint responses without significant genetic instability (i.e., polyploid cell populations were not observed). Nuclear p53 protein levels and DNA binding activity increased only after high doses of IR (>1200 cGy). Disruption of p53 responses in U1-Mel cells by E6 transfection also abrogated G(0)/G(1) cell cycle checkpoint arrest responses and increased polyploidy after IR, but did not alter radiosensitivity. These data suggest that abrogation of individual components of this coordinate IR-activated transcription factor response may lead to divergent alterations in cell cycle checkpoints, genomic instability, apoptosis, and survival. Such coordinate transcription factor activation in human cancer cells is reminiscent of prokaryotic SOS responses, and further elucidation of these events should shed light on the initial molecular events in the chromosome instability phenotype.-Yang, C.-R., Wilson-Van Patten, C., Planchon, S. M., Wuerzberger-Davis, S. M., Davis, T. W., Cuthill, C., Miyamoto, S., Boothman, D. A. Coordinate modulation of Sp1, NF-kappa B, and p53 in confluent human malignant melanoma cells after ionizing radiation.

The DNA mismatch repair gene hMLH1 is reported to function in mutation avoidance, cell cycle checkpoint control, the cytotoxicity of various DNA-damaging agents, and transcription-coupled nucleotide excision repair. Formal proof of the involvement of hMLH1 in these processes requires single gene complementation. We have stably expressed hMLH1 from a transfected cDNA in Mlh1-deficient mouse embryonic fibroblasts. Expression of hMLH1 restored normal levels of mPMS2 protein, reduced spontaneous base substitution and microsatellite mutations, increased sensitivity to the toxic effects of 6-thioguanine (6-TG), and restored 6-TG-induced cell cycle arrest. Our studies confirm that hMLH1 has an essential role in the maintenance of genomic stability and the potentiation of 6-TG cytotoxicity and provide a system for detailed structure/function analysis of the hMLH1 protein.

A role for the Mut L homologue-1 (MLH1) protein, a necessary component of DNA mismatch repair (MMR), in G2-M cell cycle checkpoint arrest after 6-thioguanine (6-TG) exposure was suggested previously. A potential role for MLH1 in G1 arrest and/or G1-S transition after damage was, however, not discounted. We report that MLH1-deficient human colon carcinoma (HCT116) cells showed decreased survival and a concomitant deficiency in G2-M cell cycle checkpoint arrest after ionizing radiation (IR) compared with genetically matched, MMR-corrected human colon carcinoma (HCT116 3-6) cells. Similar responses were noted between murine MLH1 knockout compared to wild-type primary embryonic fibroblasts. MMR-deficient HCT116 cells or embryonic fibroblasts from MLH1 knockout mice also demonstrated classic DNA damage tolerance responses after 6-TG exposure. Interestingly, an enhanced p53 protein induction response was observed in HCT116 3-6 (MLH1+) compared with HCT116 (MLH1-) cells after IR or 6-TG. Retroviral vector-mediated expression of the E6 protein did not, however, affect the enhanced G2-M cell cycle arrest observed in HCT116 3-6 compared with MLH1-deficient HCT116 cells. A role for MLH1 in G2-M cell cycle checkpoint control, without alteration in G1, after IR was also suggested by similar S-phase progression between irradiated MLH1-deficient and MLH1-proficient human or murine cells. Introduction of a nocodazole-induced G2-M block, which corrected the MLH1-mediated G2-M arrest deficiency in HCT116 cells, clearly demonstrated that HCT116 and HCT116 3-6 cells did not differ in G1 arrest or G1-S cell cycle transition after IR. Thus, our data indicate that MLH1 does not play a major role in G1 cell cycle transition or arrest. We also show that human MLH1 and MSH2 steady-state protein levels did not vary with damage or cell cycle changes caused by IR or 6-TG. MLH1-mediated G2-M cell cycle delay (caused by either MMR proofreading of DNA lesions or by a direct function of the MLH1 protein in cell cycle arrest) may be important for DNA damage detection and repair prior to chromosome segregation to eliminate carcinogenic lesions (possibly brought on by misrepair) in daughter cells.

Hereditary nonpolyposis colorectal cancer is a cancer susceptibility syndrome that has been found to be caused by mutations in any of several genes involved in DNA mismatch repair, including hMSH2, hMLH1, or hPMS2. Recent reports have suggested that hMSH2 and hMLH1 have a role in the regulation of the cell cycle. To determine if these genes are cell cycle regulated, we examined their mRNA and protein levels throughout the cell cycle in IMR-90 normal human lung fibroblasts. We demonstrate that the levels of hMSH2 mRNA and protein do not change appreciably throughout the cell cycle. Although hMLH1 mRNA levels remained constant, there was a modest (approximately 50%) increase in its protein levels during late G1 and S phase. The levels of hPMS2 mRNA fluctuated (decreasing 50% in G1 and increasing 50% in S phase), whereas hPMS2 protein levels increased 50% in late G1 and S phase. Our data indicate that, at least in normal cells, the machinery responsible for the detection and repair of mismatched DNA bases is present throughout the cell cycle.