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Introduction: The Institute of Medicine currently recommends all cancer survivors be provided survivorship care plans (SCPs) to aid them in their transition from cancer patient to cancer survivor. To our knowledge, there are very few comprehensive cancer treatment centers that report having a system that insures all patients will receive SCPs. One of the chief obstacles in broadly providing care plans is logistical; not all breast cancer patients undergo the same treatment progression and thus it is difficult to identify a suitable time after which the provider should distribute SCPs. Though adjuvant treatment pathways differ between patients, nearly all breast cancer patients receive surgery and thus surgery clinics could provide an opportunity to identify the majority of patients who will eventually be cancer survivors. The purpose of this study is to assess the feasibility of providing SCPs to breast cancer survivors by enrolling them at the postoperative visit and tracking them prospectively throughout their treatment. Methods: 75 English-speaking women over the age of 18 with stage I-III breast cancer were enrolled at their postoperative appointment. The participants' treatment progress was tracked through the electronic medical record; the treatment information was abstracted from the records and used to create treatment summaries. Once treatment was completed, participants received the SCP during one of their scheduled follow-up appointments. Results: Accrual occurred during 42 clinic days between April 2011 and February 2012. During that time, there were 129 postoperative appointments for patients with a diagnosis of breast cancer. 54 did not meet the eligibility requirements; 46 were DCIS, three had metastatic cancer, and five did not speak English. Of the patients who met the eligibility requirements 100% agreed to participate. Characteristics are shown in Table 1. Only 39.4% of participants received both chemotherapy and radiation and 9.6% of our participants received their adjuvant therapy outside of Smilow Cancer Center. Conclusion: Women recently diagnosed with breast cancer are interested in receiving survivorship care plans after treatment, as demonstrated by 100% accrual rate of eligible patients approached in the postoperative visit. The postoperative visit in a surgical clinic may provide the starting point for tracking a patient through treatment. [ABSTRACT FROM AUTHOR]

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab-deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2 - Immune - DNA repair deficiency - subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2 - Immune - DNA repair deficiency - signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379 ., Competing Interests: Competing interests: J.L.M. reports institutional research funding from AstraZeneca, Seagen, Sermonix and Olema and advisory and consulting roles with Pfizer, Seagen, Sermonix, Novartis, Stemline, AstraZeneca, Olema, GlaxoSmithKline and GE Healthcare. C.Y. reports institutional research grant from NCI/NIH; salary support and travel reimbursement from QLHC; a United States patent titled ‘Breast cancer response prediction subtypes’ (no. 18/174,491); and University of California Inventor Share. H.S.R. reports institutional research support from AstraZeneca, Daiichi Sankyo, Inc., F. Hoffmann–La Roche AG/Genentech, Inc., Gilead Sciences, Inc., Lilly; Merck and Co., Novartis Pharmaceuticals Corporation, Pfizer, Stemline Therapeutics, OBI Pharma, Ambrx, Greenwich Pharma; and advisory and consulting roles with Chugai, Puma, Sanofi, Napo and Mylan. R.N. reports research funding from Arvinas, AstraZeneca, BMS, Corcept Therapeutics, Genentech/Roche, Gilead, GSK, Merck, Novartis, OBI Pharma, OncoSec, Pfizer, Relay, Seattle Genetics, Sun Pharma and Taiho and advisory roles with AstraZeneca, BeyondSpring, Daiichi Sankyo, Exact Sciences, Fujifilm, GE, Gilead, Guardant Health, Infinity, iTeos, Merck, Moderna, Novartis, OBI, OncoSec, Pfizer, Sanofi, Seagen and Stemline. M.D. reports research grants from NIH/NCI and NIH/NIA, and contracts from PCORI. A.J.C. reports institutional research funding from Merck, Amgen, Puma, Seagen, Pfizer and Olema and advisory roles with AstraZeneca and Genentech. A.Z. reports institutional research funding from Merck, honoraria for Medscape and participation on Pfizer Advisory Board. A.S.C. reports institutional research funding from Novartis and Lilly. A.D.E. reports support from Scorpion, Infinity and Deciphera. E.S.-R. reports grants from V Foundation, NIH, Susan G. Komen; institutional research funding from GSK, Seagen, Pfizer, Lilly; consulting and honoraria from Novartis, Merck, Seagen, AstraZeneca, Lilly; Cancer Awareness Network Board member and support from ASCO and NCCN. J.C.B. reports institutional research funding from Eli Lilly and SymBioSis, participation on the Data Safety Monitoring Committee of Cairn Surgical and honoraria from PER, PeerView, OncLive, EndoMag and UpToDate. C.V. reports institutional research funding from Pfizer, Seagen, H3 Biomedicine/Eisai, AstraZeneca, CytomX; research funding to previous institution from Genentech, Roche, Pfizer, Incyte, Pharmacyclics, Novartis, TRACON Pharmaceuticals, Innocrin Pharmaceuticals, Zymeworks and H3 Biomedicine; advisory and consulting roles with Guidepoint, Novartis, Seagen, Daiichi Sankyo, AstraZeneca and Cardinal Health; unpaid consulting with Genentech; and participation in non-CME activity with Gilead, AstraZeneca. C.O. reports consulting fees from AstraZeneca, Guardant Health and Jazz Pharmaceuticals. K.S.A. reports institutional research funding from AstraZeneca, Daiichi Sankyo, Seattle Genetics and QLHC; Independent Data and Safety Monitoring committee at Seattle Genetics. K.M.K. reports advisory and consultant roles for Eli Lilly, Pfizer, Novartis, AstraZeneca, Daiichi Sankyo, Puma, 4D Pharma, OncoSec, Immunomedics, Merck, Seagen, Mersana, Menarini Silicon Biosystems, Myovant, Takeda, Biotheranostics, Regor, Gilead, Prelude Therapeutics, RayzeBio, eFFECTOR Therapeutics and Cullinan Oncology; and reports institutional research funding from Genentech/Roche, Novartis, Eli Lilly, AstraZeneca, Daiichi Sankyo and Ascentage. C.I. reports institutional research funding from Tesaro/GSK, Seattle Genetics, Pfizer, AstraZeneca, BMS, Genentech, Novartis and Regeneron; consultancy roles with AstraZeneca, Genentech, Gilead, ION, Merck, Medscape, MJH Holdings, Novartis, Pfizer, Puma and Seagen; and royalties from Wolters Kluwer (UptoDate) and McGraw Hill (Goodman and Gillman). J.T. serves as institutional principal investigator for clinical trial with Intuitive Surgical; editor lead for ABS, CGSO, SCORE, Breast Education Committee Track Leader, ASCO SESAP 19 and Breast Co-Chair, ACS. A.T. owns stock at Johnson and Johnsons, Gilead, Bristol Myers Squibb, reports participation on Pfizer Advisory Board: AstraZeneca and reports institutional research funding from Merck and Sanofi and royalties from UptoDate. R.B. reports a consultancy role at Genentech and stock ownership at Cerus Corp. K.Y. received research support unrelated to this work and paid to the institution from Pfizer, Gilead, Seagen, Dantari Pharmaceuticals, Treadwell Therapeutics, and Relay Therapeutics; support from American Cancer Society IRG grant no. IRG-19-230-48-IRG, UC San Diego Moores Cancer Center, Specialized Cancer Center support grant NIH/NCI P30CA023100, Curebound Discovery Award (2023, 2024). T.S. reports honoraria from Hologic. L.P. reports institutional research funding from Susan Komen Foundation, Breast Cancer Research Foundation, NCI, Pfizer, AstraZeneca, Menarini/Stemline, Bristol Myers Squibb, Merck and Co.; consulting fees from AstraZeneca, Merck, Novartis, Genentech, Natera, Personalis, Exact Sciences and Stemline/Menarini; patent titled ‘Method of measuring residual cancer and predicting patient survival’ (no. 7711494); and Data and Safety Monitoring Board member of the DYNASTY Breast02, OPTIMA and PARTNER trials. M.S.T. reports institutional research funding from Lilly, Gilead Sciences, Phoenix Molecular Designs, AstraZeneca, Regeneron, Merck and Novartis. A.L.A., P.B. and P.N. are employees of QLHC. G.L.H. reports institutional research grant from NIH (1R01CA255442). W.F.S. reports shares of IONIS Pharmaceuticals and Eiger Biopharmaceuticals, received consulting fees from AstraZeneca, is a cofounder with equity in Delphi Diagnostics and issued patents for (1) a method to calculate residual cancer burden and (2) genomic signature to measure sensitivity to endocrine therapy. J.P. reports honoraria from Methods in Clinical Research—faculty SCION workshop; support from ASCO and advocate scholarship; AACR—SSP program; VIVLI, U Wisc SPORE—EAB, QuantumLEAD—COVID DSMB, PCORI—reviewer and I-SPY advocate lead. P.P. reports institutional research funding from Genentech/Roche, Fabre-Kramer, Advanced Cancer Therapeutics, Caris Centers of Excellence, Pfizer, Pieris Pharmaceuticals, Cascadian Therapeutics, Bolt, Byondis, Seagen, Orum Therapeutics and Carisma Therapeutics; consulting fees from Personalized Cancer Therapy, OncoPlex Diagnostics, Immunonet BioSciences, Pfizer, HERON, Puma Biotechnology, Sirtex, CARIS Life sciences, Juniper, Bolt Biotherapeutics and AbbVie; honoraria from DAVA Oncology, OncLive/MJH Life Sciences, Frontiers—publisher, SABCS and ASCO; Speakers’ Bureau: Genentech/Roche (past); United States patent no. 8486413, United States patent no. 8501417, United States patent no. 9023362, United States patent no. 9745377; uncompensated roles with Pfizer, Seagen and Jazz. R.A.S. reports institutional research funding from OBI Pharma, QLHC, AstraZeneca and Gilead, serves on AstraZeneca and Stemline Advisory Boards and Gilead Speaker’s Bureau and reports consultancy role with QLHC. A.D. reports institutional research funding from Novartis, Pfizer, Genentech and NeoGenomics; Program Chair, Scientific Advisory Committee, ASCO. D.Y. reports research funding from NIH/NCI P30 CA 077598, P01 CA234228-01 and R01CA251600, consulting fees from Martell Diagnostics, and honoraria and travel for speaking at the ‘International Breast Cancer Conference.’ L.J.v.V. is a founding advisor and shareholder of Exai Bio and is a part-time employee and owns stock in Agendia. N.M.H. reports institutional research funding from NIH. L.J.E. reports funding from Merck and Co., participation on an advisory board for Blue Cross Blue Shield and personal fees from UpToDate and is an unpaid board member of QLHC. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin-cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin-cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.ClinicalTrials.gov registration: NCT01042379 ., Competing Interests: Competing interests: R.A.S. reports institutional research funding from OBI Pharma, QLHC, AstraZeneca and Gilead; serves on AstraZeneca and Stemline Advisory Boards and Gilead Speaker’s Bureau; and has a consultancy role with QLHC. M.S.T. reports institutional research funding from Lilly, Gilead Sciences, Phoenix Molecular Designs, AstraZeneca, Regeneron, Merck and Novartis. C.Y. reports institutional research grant from NCI/NIH; salary support and travel reimbursement from QLHC; US patent titled, ‘Breast cancer response prediction subtypes’ (no. 18/174,491); and University of California Inventor Share. R.N. reports research funding from Arvinas, AstraZeneca, BMS, Corcept Therapeutics, Genentech/Roche, Gilead, GSK, Merck, Novartis, OBI Pharma, OncoSec, Pfizer, Relay, Seattle Genetics, Sun Pharma and Taiho Oncology and advisory roles with AstraZeneca, BeyondSpring, Daiichi Sankyo, Exact Sciences, Fujifilm, GE, Gilead, Guardant Health, Infinity, iTeos, Merck, Moderna, Novartis, OBI, OncoSec, Pfizer, Sanofi, Seagen and Stemline. H.S.R. reports institutional research support from AstraZeneca, Daiichi Sankyo, F. Hoffmann-La Roche AG/Genentech, Gilead Sciences, Lilly, Merck & Co., Novartis Pharmaceuticals Corporation, Pfizer, Stemline Therapeutics, OBI Pharma, Ambrx and Greenwich Pharma and has advisory and consulting roles with Chugai, Puma, Sanofi, Napo and Mylan. M.D. reports research grants from NIH/NCI and NIH/NIA, and contracts from PCORI. A.J.C. reports institutional research funding from Merck, Amgen, Puma, Seagen, Pfizer and Olema and has advisory roles with AstraZeneca and Genentech. E.S.-R. reports grants from V Foundation, NIH and Susan G. Komen; institutional research funding from GSK, Seagen, Pfizer and Lilly; and consulting and honoraria from Novartis, Merck, Seagen, AstraZeneca and Lilly; is a Cancer Awareness Network Board member and receives support from ASCO and NCCN. J.C.B. reports institutional research funding from Eli Lilly and SymBioSis, participation on the Data Safety Monitoring Committee of Cairn Surgical and honoraria from PER, PeerView, OncLive, EndoMag and UpToDate. C.O. reports consulting fees from AstraZeneca, Guardant Health and Jazz Pharmaceuticals. K.K. reports advisory and consultant roles for Eli Lilly, Pfizer, Novartis, AstraZeneca, Daiichi Sankyo, Puma, 4D Pharma, OncoSec, Immunomedics, Merck, Seagen, Mersana, Menarini Silicon Biosystems, Myovant, Takeda, Biotheranostics, Regor, Gilead, Prelude Therapeutics, RayzeBio, eFFECTOR Therapeutics and Cullinan Oncology and reports institutional research funding from Genentech/Roche, Novartis, Eli Lilly, AstraZeneca, Daiichi Sankyo and Ascentage. A.D.E. reports support from Scorpion, Infinity and Deciphera. C.V. reports institutional research funding from Pfizer, Seagen, H3 Biomedicine/Eisai, AstraZeneca and CytomX; research funding to their previous institution from Genentech, Roche, Pfizer, Incyte, Pharmacyclics, Novartis, TRACON Pharmaceuticals, Innocrin Pharmaceuticals, Zymeworks and H3 Biomedicine; advisory and consulting roles with Guidepoint, Novartis, Seagen, Daiichi Sankyo, AstraZeneca and Cardinal Health; unpaid consulting with Genentech; and participation in non-CME activity with Gilead and AstraZeneca. N.W. reports participation on Gilead’s Advisory Board and honoraria from OncLive, NCCN and Total Health Conferencing. K.S.A. reports institutional research funding from AstraZeneca, Daiichi Sankyo, Seattle Genetics, QLHC and the IDSM committee at Seattle Genetics. A.S.C. reports institutional research funding from Novartis and Lilly. C.F. reports honoraria from Curio Science and OncLive and institutional research funding from Eli Lily. C.I. reports institutional research funding from Tesaro/GSK, Seattle Genetics, Pfizer, AstraZeneca, BMS, Genentech, Novartis and Regeneron; consultancy roles with AstraZeneca, Genentech, Gilead, ION, Merck, Medscape, MJH Holdings, Novartis, Pfizer, Puma and Seagen; and royalties from Wolters Kluwer (UpToDate) and McGraw Hill (Goodman and Gilman). A.T. owns stock at Johnson & Johnson, Gilead, Bristol Myers Squibb; reports participation on Pfizer’s Advisory Board: AstraZeneca; reports institutional research funding from Merck and Sanofi; and has royalties from UpToDate. J.T. serves as institutional principal investigator for clinical trial with Intuitive Surgical and is the Editor Lead for ABS, CGSO, SCORE, Breast Education Committee Track Leader, ASCO SESAP 19 and Breast Co-Chair, ACS. K.Y. received research support unrelated to this work and paid to the institution from Pfizer, Gilead, Seagen, Dantari Pharmaceuticals, Treadwell Therapeutics and Relay Therapeutics and support from American Cancer Society IRG grant (no. IRG-19-230-48-IRG), UC San Diego Moores Cancer Center, Specialized Cancer Center support grant NIH/NCI (P30CA023100) and Curebound Discovery Award (2023, 2024). L.H. reports advisory and consultancy roles with Pfizer, and AstraZeneca. K.G. reports participation in advisory boards with honoraria to the institution from AstraZeneca, Novartis, Puma Biotechnologies, Eli Lilly, Gilead, Exact Sciences, NeoGenomics and TerSera Therapeutics. F.M.H. reports consultancy for Novartis. T.S. reports honoraria from Hologic. A.L.A., P.B. and P.N. are employees of QLHC. G.L.H. reports an institutional research grant from NIH (1R01CA255442). W.F.S. reports shares in IONIS Pharmaceuticals and Eiger Biopharmaceuticals; received consulting fees from AstraZeneca; is a cofounder with equity in Delphi Diagnostics; and issued patents for: (1) a method to calculate residual cancer burden, and (2) genomic signature to measure sensitivity to endocrine therapy. J.P. reports honoraria from Methods in Clinical Research (Faculty SCION Workshop) and support from ASCO and Advocate Scholarship; AACR (SSP Program); and VIVLI, U Wisc SPORE (EAB), QuantumLEAD (COVID DSMB), PCORI; is a reviewer; and is an I-SPY advocate lead. P.P. reports institutional research funding from Genentech/Roche, Fabre-Kramer, Advanced Cancer Therapeutics, Caris Centers of Excellence, Pfizer, Pieris Pharmaceuticals, Cascadian Therapeutics, Bolt, Byondis, Seagen, Orum Therapeutics and Carisma Therapeutics; consulting fees from Personalized Cancer Therapy, OncoPlex Diagnostics, Immunonet BioSciences, Pfizer, HERON, Puma Biotechnology, Sirtex, Caris Life Sciences, Juniper, Bolt Biotherapeutics and AbbVie; honoraria from Dava Oncology, OncLive/MJH Life Sciences, Frontiers (Publisher), SABCS and ASCO; Speakers’ Bureau: Genentech/Roche (past); and US patent no. 8,486,413, US patent no. 8,501,417, US patent no. 9,023,362 and US patent no. 9,745,377; and uncompensated roles with Pfizer, Seagen and Jazz. A.D.M. reports institutional research funding from Novartis, Pfizer, Genentech and NeoGenomics and is a program chair of the Scientific Advisory Committee, ASCO. D.Y. reports research funding from NIH/NCI: P30CA 077598, P01CA234228-01 and R01CA251600; consulting fees from Martell Diagnostics; and honoraria and travel for speaking at the ‘International Breast Cancer Conference’. L.J.v.V. is a founding advisor and shareholder of Exai Bio and is a part-time employee and owns stock in Agendia. N.M.H. reports institutional research funding from NIH. L.J.E. reports funding from Merck & Co., participation on an advisory board for Blue Cross Blue Shield, and personal fees from UpToDate and is an unpaid board member of QLHC. All other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Following treatment, cancer survivors often experience pain that negatively impacts their quality of life. Although both anxiety and fear of cancer recurrence (FCR) have been shown to exacerbate pain interference, less is known about either the temporal relationship between anxiety/FCR and pain interference or modifiable cognitive/emotional factors that might moderate that relationship among cancer survivors. This longitudinal study aims to advance our understanding of the impact of both anxiety and FCR following primary cancer treatment on subsequent pain interference. We also examined potentially modifiable moderators (i.e., cancer-related illness beliefs and emotion regulation difficulties) of the relationship between anxiety/FCR and subsequent pain interference. Adults (N = 397; 67% female; M age = 59.1 years) diagnosed with breast, colorectal, or prostate cancer completed self-report measures at baseline (average of 2.5 months following treatment completion) and at 6-month follow-up. Both greater anxiety and FCR not only predicted subsequent pain interference, but also predicted increases in pain interference over time. Additionally, complex interaction patterns were observed between anxiety and the potential moderators on pain interference. Specifically, lower Personal Control beliefs and higher Consequences beliefs were associated with greater pain interference for those with lower levels of anxiety/FCR. Emotion regulation difficulties also moderated the anxiety-pain interference link (i.e., was more strongly associated with greater pain interference at lower levels of anxiety), but not the FCR-pain link. Chronicity beliefs did not interact with anxiety or FCR in predicting pain interference. This study advances our understanding of the role of anxiety/FCR on pain interference over time as well as potential psychological treatment targets for individuals at greater risk for longer-term pain following cancer treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Weight gain after breast cancer diagnosis is associated with adverse health outcomes. Yet, few studies have characterized post-diagnosis weight change in the modern treatment era or populations most at risk for weight changes. Among women diagnosed with stages I-III breast cancer in the Smilow Care Network (2013-2019; N = 5441), we abstracted demographic and clinical characteristics from electronic health records and survival data from tumor registries. We assessed if baseline characteristics modified weight trajectories with nonlinear multilevel mixed-effect models. We evaluated body mass index (BMI) at diagnosis and weight change 1-year post-diagnosis in relation to all-cause and breast cancer-specific mortality with Cox proportional hazard models. Women had 34.4 ± 25.5 weight measurements over 3.2 ± 1.8 years of follow-up. Weight gain was associated with ER/PR-, HER2+ tumors, BMI ≤ 18.5 kg/m 2 , and age ≤ 45 years (+4.90 kg (standard error [SE] = 0.59), +3.24 kg (SE = 0.34), and +1.75 kg (SE = 0.10), respectively). Weight loss was associated with BMI ≥ 35 kg/m 2 and age ≥ 70 years (-4.50 kg (SE = 0.08) and -4.34 kg (SE = 0.08), respectively). Large weight loss (≥10%), moderate weight loss (5-10%), and moderate weight gain (5-10%) 1-year after diagnosis were associated with higher all-cause mortality (hazard ratio [HR] = 2.93, 95% confidence interval [CI] = 2.28-3.75, HR = 1.32, 95% CI = 1.02-1.70 and HR = 1.39, 95% CI = 1.04-1.85, respectively). BMI ≥ 35 kg/m 2 or BMI ≤ 18.5 kg/m 2 at diagnosis were also associated with higher all-cause mortality. Weight change after a breast cancer diagnosis differed by demographic and clinical characteristics highlighting subgroups at-risk for weight change during a 5-year period post-diagnosis. Monitoring and interventions for weight management early in clinical care are important., (© 2023. The Author(s).)

Background: Lifestyle interventions for breast cancer survivors have proved effective at stimulating positive behavior change and promoting healthy weight loss, although integrating these programs into clinical practice is challenging. We evaluated the effect of a 6-month, unsupervised, self-guided, lifestyle intervention using printed materials and online videos vs. waitlist group on body weight for breast cancer survivors. Methods: The Lifestyle, Exercise and Nutrition (LEAN) Self-Guided trial randomized breast cancer survivors with a body mass index ≥25 kg/m 2 to a 6-month lifestyle intervention (N = 102) or waitlist group (N = 103). Effects of the intervention on self-reported body weight, physical activity (PA), diet quality (via Health Eating Index-2010 (HEI-2010)), and quality of life were assessed using mixed model repeated measures analysis. Results: At 6 months, the intervention arm had significantly greater weight loss compared with the waitlist group (mean difference = -1.3 kg, 95% confidence interval [CI] = -2.5, -0.13). We observed suggestive improvements in PA (mean difference = 18.7 min/week, 95% CI = -24.2, 61.6), diet quality (mean difference in HEI = 3.2 points, 95% CI = -0.20, 6.5), and fatigue (mean difference in Functional Assessment of Chronic Illness Therapy-Fatigue scale = 1.4 points, 95% CI = -1.1, 3.9). Conclusions: The LEAN Self-Guided intervention led to favorable weight changes over 6 months. Low-resource-intensive programs have the potential to be delivered in diverse healthcare settings and may support breast cancer survivors in achieving a healthy body weight.

Purpose: Extending adjuvant endocrine therapy (ET) beyond the standard 5 years offers added protection against late breast cancer recurrences in women with early-stage hormone receptor-positive (HR +) breast cancer. Little is known about treatment persistence to extended ET (EET) and the role that genomic assays may play. In this study, we evaluated persistence to EET in women who had Breast Cancer Index (BCI) testing., Methods: Women with stage I-III HR + breast cancer who had BCI testing after at least 3.5 years of adjuvant ET and ≥ 7 years of follow-up after diagnosis were included (n = 240). Data on medication persistence was based on prescriptions in the electronic health record., Results: BCI predicted 146 (61%) patients to have low - BCI (H/I)-low - and 94 (39%) patients to have high likelihood of benefit from EET (BCI (H/I)-high). Continuation of ET after BCI occurred in 76 (81%) (H/I)-high and 39 (27%) (H/I)-low patients. Non-persistence rates were 19% in the (H/I)-high and 38% in the (H/I)-low group. The most common reason for non-persistence was intolerable side effects. Patients on EET underwent more DXA bone density scans than those who stopped ET at 5 years (mean 2.09 versus 1.27; p < 0.001). At a median follow-up of 10 years from diagnosis, there were 6 metastatic recurrences., Conclusions: In patients who continued ET after BCI testing, the rates of persistence to EET were high, particularly in patients with predicted high likelihood of benefit from EET. Use of EET is associated with increased use of DXA scans., (© 2023. The Author(s).)

Cancer cells cannot proliferate without sufficient energy to generate biomass for rapid cell division, as well as to fuel their functions at baseline. For this reason, many recent observational and interventional studies have focused on increasing energy expenditure and/or reducing energy intake during and after cancer treatment. The impact of variance in diet composition and in exercise on cancer outcomes has been detailed extensively elsewhere and is not the primary focus of this review. Instead, in this translational, narrative review we examine studies of how energy balance impacts anticancer immune activation and outcomes in triple-negative breast cancer (TNBC). We discuss preclinical, clinical observational, and the few clinical interventional studies on energy balance in TNBC. We advocate for the implementation of clinical studies to examine how optimizing energy balance-through changes in diet and/or exercise-may optimize the response to immunotherapy in people with TNBC. It is our conviction that by taking a holistic approach that includes energy balance as a key factor to be considered during and after treatment, cancer care may be optimized, and the detrimental effects of cancer treatment and recovery on overall health may be minimized., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Few trials have examined the effect of lifestyle behavioral interventions on tissue markers in patients with cancer. The purpose of this study was to examine the feasibility and impact of a 6-month weight loss intervention on breast tissue and serum biomarkers in women with breast cancer. Fifty-one women who completed breast cancer treatment and had a BMI ≥ 25.0 kg/m 2 were randomized to a weight loss intervention or usual care. Breast tissue biopsies, fasting blood draw and body composition were collected at baseline and 6 months, with between-group changes examined using analysis of covariance method. Baseline and post-intervention biopsies were conducted in 49 and 42 women, respectively, with pre- and post-epithelial tissue available from 25 tissue samples. Average 6-month weight loss was 6.7% for the weight loss group and 2.0% increase for the usual care group (p < 0.0001). At baseline, body fat and serum insulin levels were inversely associated with breast tissue insulin receptor levels and CD68 (p < 0.05). At 6 months, favorable changes were observed in serum leptin and adiponectin levels and tissue CD163 among women randomized to weight loss vs. adverse change in women randomized to usual care (p < 0.05). Breast tissue biopsies are feasible to collect in a clinical research setting among breast cancer survivors, with weight loss favorably impacting metabolic and inflammatory markers associated with breast cancer., (© 2022. The Author(s).)

The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.

Lifestyle interventions among breast cancer survivors with obesity have demonstrated successful short-term weight loss, but data on long-term weight maintenance are limited. We evaluated long-term weight loss maintenance in 100 breast cancer survivors with overweight/obesity in the efficacious six-month Lifestyle, Exercise, and Nutrition (LEAN) Study (intervention = 67; usual care = 33). Measured baseline and six-month weights were available for 92 women. Long-term weight data were obtained from electronic health records. We assessed weight trajectories between study completion (2012-2013) and July 2019 using growth curve analyses. Over up to eight years (mean = 5.9, SD = 1.9) of post-intervention follow-up, both the intervention ( n = 60) and usual care ( n = 32) groups declined in body weight. Controlling for body weight at study completion, the yearly weight loss rate in the intervention and usual care groups was -0.20 kg (-0.2%/year) (95% CI: 0.06, 0.33, p = 0.004) and -0.32 kg (-0.4%/year) (95% CI: 0.12, 0.53, p = 0.002), respectively; mean weight change did not differ between groups ( p = 0.31). It was encouraging that both groups maintained their original intervention period weight loss (6% intervention, 2% usual care) and had modest weight loss during long-term follow-up. Breast cancer survivors in the LEAN Study, regardless of randomization, avoided long-term weight gain following study completion.

Purpose: Standard-of-care treatment for metastatic hormone receptor-positive (HR + ), HER2-negative (HER2 - ) breast cancer includes endocrine therapy (ET) combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Optimal treatment after progression on CDK4/6i is unknown. The TRINITI-1 trial investigated ribociclib, a CDK4/6i that has recently demonstrated significant overall survival benefit in two phase III trials, in combination with everolimus and exemestane in patients with HR + , HER2 - advanced breast cancer (ABC) after progression on a CDK4/6i., Patients and Methods: This multicenter, open-label, single-arm, phase I/II study included patients with locally advanced/metastatic HR + /HER2 - breast cancer. The primary endpoint was clinical benefit rate (CBR) at week 24 among patients with ET-refractory disease with progression on a CDK4/6i. Other endpoints included safety and biomarker analysis., Results: Of 104 patients enrolled (phases I and II), 96 had prior CDK4/6i. Recommended phase II doses (all once daily days 1-28 of 28-day cycle) were ribociclib 300 mg, everolimus 2.5 mg, and exemestane 25 mg (group 1) and ribociclib 200 mg, everolimus 5 mg, and exemestane 25 mg (group 2). CBR among 95 efficacy-evaluable patients (phases I and II) at week 24 was 41.1% (95% confidence interval, 31.1-51.6), which met the primary endpoint (predetermined threshold: 10%). Common adverse events included neutropenia (69.2%) and stomatitis (40.4%). No new safety signals were observed; no grade 3/4 QTc prolongation was reported., Conclusions: Preliminary TRINITI-1 safety and efficacy results support further investigation of CDK4/6 blockade and targeting of the PI3K/AKT/mTOR signaling pathway in patients with ET-refractory HR + /HER2 - ABC after progression on a CDK4/6i., (©2021 American Association for Cancer Research.)

Obesity among breast cancer survivors is associated with increased risk for recurrence and mortality. The hormone ghrelin plays a role in initiating appetite and thus regulating body weight. This study aims to determine the effect of a lifestyle intervention on ghrelin levels in breast cancer survivors with a body mass index (BMI) ≥ 25 kg/m 2 . The Lifestyle, Exercise, and Nutrition (LEAN) study was a 6-month randomized trial, examining the effectiveness of a weight loss intervention versus usual care in 151 breast cancer survivors with BMI ≥ 25 kg/m 2 . Ghrelin was measured in fasting baseline and 6-month blood samples. Baseline associations between ghrelin, body composition, and blood biomarkers were examined. Six-month change in ghrelin was compared between study arms. Ghrelin measurements were available for 149 women. At baseline, ghrelin was correlated with age (r = 0.28, p < 0.001) and inversely correlated with weight (r = -0.18, p = 0.03), lean body mass (r = -0.18, p = 0.02), and leptin (r = -0.18, p = 0.03). Over 6 months, ghrelin increased by 144 pg/mL (7.2%) in the intervention and decreased by 466 pg/mL (32.5%) in the usual care (p = 0.07). Among all women, greater weight loss was associated with an increase in ghrelin (p = 0.01). These findings indicate that weight loss, achieved through a lifestyle intervention, is associated with higher ghrelin levels in breast cancer survivors which may be informative for developing sustainable weight loss programming for this population. Future research should investigate the long term impacts of lifestyle interventions on ghrelin levels in the context of weight maintenance and weight regain.

Observational studies report that physical activity and metformin are associated with improved clinical outcome in patients with cancer. Inflammation is one biological mechanism hypothesized to mediate these associations. In this phase II, multicenter, 2 × 2 factorial trial, 139 patients with breast and colorectal cancer who completed standard therapy were randomized to one of four treatment groups for 12 weeks: exercise alone, metformin alone, exercise and metformin, or control. Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), soluble tumor necrosis factor alpha receptor two (sTNFαR2), and IL6. The primary modeling strategy evaluated the trial product estimand that was quantified using a generalized linear mixed model. Compared with control, exercise alone reduced hs-CRP [-30.2%; 95% confidence interval (CI), -50.3, -1.0] and IL6 (-30.9%; 95% CI, -47.3, -9.5) but did not change sTNFαR2 (1.0%; 95% CI, -10.4, 13.9). Compared with control, metformin alone did not change hs-CRP (-13.9%; 95% CI, -40.0, 23.4), sTNFαR2 (-10.4%; 95% CI, -21.3, 2.0), or IL6 (-22.9%; 95% CI, -42.3, 2.0). Compared with control, exercise and metformin reduced sTNFαR2 (-13.1%; 95% CI, -22.9, -1.0) and IL6 (-38.7%; 95% CI, -52.3, -18.9) but did not change hs-CRP (-20.5%; 95% CI, -44.0, 12.7). The combination of exercise and metformin was not synergistic for hs-CRP, sTNFαR2, or IL6. In survivors of breast and colorectal cancer with low baseline physical activity and without type 2 diabetes, exercise and metformin reduced measures of inflammation that are associated with cancer recurrence and mortality., (©2020 American Association for Cancer Research.)

Background: Observational data support inverse relationships between exercise or metformin use and disease outcomes in colorectal and breast cancer survivors, although the mechanisms underlying these associations are not well understood., Methods: In a phase II trial, stage I-III colorectal and breast cancer survivors who completed standard therapy were randomly assigned to structured exercise or metformin or both or neither for 12 weeks. The primary outcome was change in fasting insulin levels; secondary outcomes included changes in other blood-based energetic biomarkers and anthropometric measurements. Analyses used linear mixed models., Results: In total, 139 patients were randomly assigned; 91 (65%) completed follow-up assessments. Fasting insulin levels statistically significantly decreased in all three intervention arms (-2.47 μU/mL combination arm, -0.08 μU/mL exercise only, -1.16 μU/mL metformin only, + 2.79 μU/mL control arm). Compared with the control arm, all groups experienced statistically significant weight loss between baseline and 12 weeks (-1.8% combination arm, -0.22% exercise only, -1.0% metformin only, +1.55% control). The combination arm also experienced statistically significant improvements in the homeostatic model assessment for insulin resistance (-30.6% combination arm, +61.2% control) and leptin (-42.2% combination arm, -0.8% control), compared with the control arm. The interventions did not change insulin-like growth factor-1 or insulin-like growth factor binding protein-3 measurements as compared with the control arm. Tolerance to metformin limited compliance (approximately 50% of the participants took at least 75% of the planned dosages in both treatment arms)., Conclusions: The combination of exercise and metformin statistically significantly improved insulin and associated metabolic markers, as compared to the control arm, with potential greater effect than either exercise or metformin alone though power limited formal synergy testing. Larger efforts are warranted to determine if such a combined modality intervention can improve outcomes in colorectal and breast cancer survivors., (© The Author(s) 2020. Published by Oxford University Press.)

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice., Competing Interests: The authors declare no competing interests.

Objective: This study examined the effect of 12 months of aerobic and resistance exercise versus usual care on changes in body composition in postmenopausal breast cancer survivors taking aromatase inhibitors (AIs)., Methods: The Hormones and Physical Exercise study enrolled 121 breast cancer survivors and randomized them to either supervised twice-weekly resistance exercise training and 150 min/wk of aerobic exercise (N = 61) or a usual care (N = 60) group. Dual-energy X-ray absorptiometry scans were conducted at baseline, 6 months, and 12 months to assess changes in body mass index, percent body fat, lean body mass, and bone mineral density., Results: At 12 months, the exercise group relative to the usual care group had a significant increase in lean body mass (0.32 vs. -0.88 kg, P = 0.03), a decrease in percent body fat (-1.4% vs. 0.48%, P = 0.03), and a decrease in body mass index (-0.73 vs. 0.17 kg/m 2 , P = 0.03). Change in bone mineral density was not significantly different between groups at 12 months (0.001 vs. -0.006 g/cm 2 , P = 0.37)., Conclusions: A combined resistance and aerobic exercise intervention improved body composition in breast cancer survivors taking AIs. Exercise interventions may help to mitigate the negative side effects of AIs and improve health outcomes in breast cancer survivors., (© 2016 The Obesity Society.)

Obesity is associated with increased breast cancer recurrence and mortality. Though some post-diagnosis weight loss interventions have achieved weight loss outcomes, it is unclear whether they also improve diet quality. In the Lifestyle, Exercise, and Nutrition (LEAN) study, overweight or obese breast cancer survivors were randomized to either usual care group ( n =33) or the 6-month lifestyle intervention ( n =67). Dietary intake was assessed at baseline and 6 months using a validated food frequency questionnaire, and overall diet quality was calculated using the Healthy Eating Index (HEI)-2010 (range 0-100). Intervention effects on diet were evaluated with generalized linear models. Among the 81 participants (51 intervention, 30 usual care) with dietary data, the mean baseline HEI score was 70.5 (s.d.=8.8) and was improved at 6 months (intervention group=6.8 point increase vs usual care=3.1, P =0.09). Intervention group participants achieved greater reductions in percent of energy from total fat (-4.2% vs -1.2%; P =0.013) and saturated fat (-2.2% vs -1.1%; P =0.003), and greater increases in fiber (4.8 g per 1000 kcal vs 1.3 g per 1000 kcal; P =0.007) and fruit (0.5 servings vs 0.0 servings; P =0.006) intake. Intervention group participants who lost ⩾5% body weight ( n =27) demonstrated significantly greater improvements in HEI score (10.4 vs 2.8) than those who lost <5% ( n =23). The intervention increased fruit and fiber intake and decreased percent energy from fat, and those with greater weight loss achieved greater increases in overall diet quality. These findings support the ability of a weight loss intervention to improve diet among breast cancer survivors., Competing Interests: The authors declare no conflict of interest.

Objectives: To examine the association between time since cancer diagnosis and health-related quality of life (HRQOL) among cancer survivors in remission., Methods: Analyzing data from 3,610 cancer survivors and 59,539 individuals without cancer in the Medical Expenditure Panel Survey, we examined the relationship between time since cancer diagnosis and HRQOL, taking remission status into account and controlling for patients' demographic characteristics and comorbidities. HRQOL measurements included the six-dimensional health state short form (derived from 36-item short form health survey) (SF-6D) utility scores, the physical component summary score, and the mental component summary score., Results: The relationship between time since cancer diagnosis and HRQOL varied substantially across cancer types. Compared with individuals without cancer, survivors of breast, prostate, or poor-prognosis cancer had statistically lower SF-6D scores within 2 years of diagnosis (-0.044, -0.062, and -0.088, respectively). Breast cancer survivors had SF-6D scores similar to those of individuals without cancer after 2 years, as did patients with poor-prognosis cancer after 5 years. Nevertheless, even after a period of 10 years, survivors of prostate or cervical cancer had a lower level of SF-6D scores (-0.027 and -0.042, respectively). The comparisons of physical health between cancer survivors and individuals without cancer were similar to those of SF-6D. In contrast, most cancer survivors did not experience poorer mental health; survivors of prostate or cervical cancer, however, had lower mental component summary scores after 10 years of diagnosis., Conclusions: The level of HRQOL among cancer survivors depends on time since cancer diagnosis and cancer type. Some cancer survivors have lower HRQOL after a decade of diagnosis, even in remission., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Interpretation of complex cancer genome data, generated by tumor target profiling platforms, is key for the success of personalized cancer therapy. How to draw therapeutic conclusions from tumor profiling results is not standardized and may vary among commercial and academically-affiliated recommendation tools. We performed targeted sequencing of 315 genes from 75 metastatic breast cancer biopsies using the FoundationOne assay. Results were run through 4 different web tools including the Drug-Gene Interaction Database (DGidb), My Cancer Genome (MCG), Personalized Cancer Therapy (PCT), and cBioPortal, for drug and clinical trial recommendations. These recommendations were compared amongst each other and to those provided by FoundationOne. The identification of a gene as targetable varied across the different recommendation sources. Only 33% of cases had 4 or more sources recommend the same drug for at least one of the usually several altered genes found in tumor biopsies. These results indicate further development and standardization of broadly applicable software tools that assist in our therapeutic interpretation of genomic data is needed. Existing algorithms for data acquisition, integration and interpretation will likely need to incorporate artificial intelligence tools to improve both content and real-time status., Competing Interests: No conflicts to disclose except for exceptions below: Eric Reiner: Consulting or Advisory Role: BSCI, Surefire Medical; Other Relationship: Sirtex Medical. Sarah Schellhorn Mougalian: Stock and Other Ownership Interests: Gilead Science, Coronado Biosciences, Roche; Research Funding: Genentech. Maysa M. Abu-Khalaf: Research Funding: Novartis, Merck, Clovis Oncology, Pfizer, Genentech/Roche, Merrimack. Lajos Pusztai: Consulting or Advisory Role: Clovis Oncology, Celgene; Honoraria: BioTheranostics, Pfizer; Research Funding: Foundation Medicine, Merck, Genentech.

There is growing consensus that multigene prognostic tests provide useful complementary information to tumor size and grade in estrogen receptor (ER)-positive breast cancers. The tests primarily rely on quantification of ER and proliferation-related genes and combine these into multivariate prediction models. Since ER-negative cancers tend to have higher proliferation rates, the prognostic value of current multigene tests in these cancers is limited. First-generation prognostic signatures (Oncotype DX, MammaPrint, Genomic Grade Index) are substantially more accurate to predict recurrence within the first 5 years than in later years. This has become a limitation with the availability of effective extended adjuvant endocrine therapies. Newer tests (Prosigna, EndoPredict, Breast Cancer Index) appear to possess better prognostic value for late recurrences while also remaining predictive of early relapse. Some clinical prediction problems are more difficult to solve than others: there are no clinically useful prognostic signatures for ER-negative cancers, and drug-specific treatment response predictors also remain elusive. Emerging areas of research involve the development of immune gene signatures that carry modest but significant prognostic value independent of proliferation and ER status and represent candidate predictive markers for immune-targeted therapies. Overall metrics of tumor heterogeneity and genome integrity (for example, homologue recombination deficiency score) are emerging as potential new predictive markers for platinum agents. The recent expansion of high-throughput technology platforms including low-cost sequencing of circulating and tumor-derived DNA and RNA and rapid reliable quantification of microRNA offers new opportunities to build extended prediction models across multiplatform data.