An Unsupervised Machine Learning Approach to Evaluating the Association of Symptom Clusters With Adverse Outcomes Among Older Adults With Advanced Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Older adults with advanced cancer who have high pretreatment symptom severity often experience adverse events during cancer treatments. Unsupervised machine learning may help stratify patients into different risk groups. Objective: To evaluate whether clusters identified from baseline patient-reported symptom severity were associated with adverse outcomes. Design, Setting, and Participants: This secondary analysis of the Geriatric Assessment Intervention for Reducing Toxicity in Older Patients With Advanced Cancer (GAP70+) Trial (2014-2019) included patients who completed the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) before starting a new cancer treatment regimen and received care at community oncology sites across the United States. An unsupervised machine learning algorithm (k-means with Euclidean distance) clustered patients based on similarities of baseline symptom severities. Clustering variables included severity items of 24 PRO-CTCAE symptoms (range, 0-4; corresponding to none, mild, moderate, severe, and very severe). Total severity score was calculated as the sum of 24 items (range, 0-96). Whether the clusters were associated with unplanned hospitalization, death, and toxic effects was then examined. Analyses were conducted in January and February 2022. Exposures: Symptom severity. Main Outcomes and Measures: Unplanned hospitalization over 3 months (primary), all-cause mortality over 1 year, and any clinician-rated grade 3 to 5 toxic effect over 3 months. Results: Of 718 enrolled patients, 706 completed baseline PRO-CTCAE and were included (mean [SD] age, 77.2 [5.5] years, 401 [56.8%] male patients; 51 [7.2%] Black and 619 [87.8%] non-Hispanic White patients; 245 [34.7%] with gastrointestinal cancer; 175 [24.8%] with lung cancer; mean [SD] impaired Geriatric Assessment domains, 4.5 [1.6]). The algorithm classified 310 (43.9%), 295 (41.8%), and 101 (14.3%) into low-, medium-, and high-severity clusters (within-cluster mean [SD] severity scores: low, 6.3 [3.4]; moderate, 16.6 [4.3]; high, 29.8 [7.8]; P < .001). Controlling for sociodemographic variables, clinical factors, study group, and practice site, compared with patients in the low-severity cluster, those in the moderate-severity cluster were more likely to experience hospitalization (risk ratio, 1.36; 95% CI, 1.01-1.84; P = .046). Moderate- and high-severity clusters were associated with a higher risk of death (moderate: hazard ratio, 1.31; 95% CI, 1.01-1.69; P = .04; high: hazard ratio, 2.00; 95% CI, 1.43-2.78; P < .001), but not toxic effects. Conclusions and Relevance: In this study, unsupervised machine learning partitioned patients into distinct symptom severity clusters; patients with higher pretreatment severity were more likely to experience hospitalization and death. Trial Registration: ClinicalTrials.gov Identifier: NCT02054741.

Caregiver-oncologist prognostic concordance, caregiving esteem, and caregiver outcomes.

INTRODUCTION: Caregiver-oncologist concordance regarding the patient's prognosis is associated with worse caregiver outcomes (e.g., depressive symptoms), but mechanisms underpinning these associations are unclear. We explored whether caregiving esteem mediates these associations. METHODS: At enrollment, caregivers and oncologists used a 5-point ordinal scale to estimate patient survival; identical responses were considered concordant. At 4-6 weeks, caregivers completed an assessment of the extent to which caregiving imparts self-esteem (Caregiver Reaction Assessment self-esteem subscale; range 0-5; higher score indicates greater esteem). They also completed Patient Health Questionnaire-2 (PHQ-2) for depressive symptoms, Distress Thermometer, and 12-Item Short Form Survey for quality of life (QoL). Mediation analysis with bootstrapping (PROCESS macro by Hayes) was used to estimate the extent to which caregiving mediated the effects of prognostic concordance on caregiver outcomes through caregiving esteem. RESULTS: Prognostic concordance occurred in 28% the caregiver-oncologist dyads; 85% of the discordance were due to caregivers estimating a longer patient's survival. At 4-6 weeks, mean caregiving esteem score was 4.4 (range 1.5-5.0). Lower caregiving esteem mediated the associations of concordance with higher PHQ-2 [indirect effect = 0.12; 95% Confidence Interval (CI) 0.03, 0.27], greater distress (indirect effect =0.25; 95% CI 0.08, 0.48), and poorer QoL (indirect effect = -1.50; 95% CI -3.06, -0.41). Caregiving esteem partially mediated 39%, 64%, and 48% of the associations between caregiver-oncologist concordance and PHQ-2, distress, and SF-12, respectively. CONCLUSIONS: Caregiver-oncologist concordance was associated with lower caregiving esteem. Lower caregiving esteem mediated the negative relationship between caregiver-oncologist concordance and caregiver outcomes.

The shared uncertainty experience of older adults with advanced cancer and their caregivers.

OBJECTIVE: One primary source of psychological distress in patients with cancer and their caregivers is uncertainty. However, the uncertainty trajectory and its relationship between older adults with advanced cancer and their caregivers have rarely been examined. This study describes the uncertainty trajectory in patient-caregiver dyads, explores the effect of geriatric assessment (GA) intervention on trajectory, and examines the interdependent relationship of uncertainty. METHODS: This secondary analysis used longitudinal data from a national cluster-randomized controlled trial examining a GA intervention compared to usual care. Participants completed the modified 9-item Mishel Uncertainty in Illness Scale at enrollment, 4-6 weeks, 3 months, and 6 months. The dyadic growth model and cross-lagged actor-partner interdependence model were used. RESULTS: A total of 397 dyads (patient age M = 76.81 ± SD5.43; caregiver age M = 66.69 ± SD12.52) were included. Both had a trend of decreased uncertainty over time (b = -0.16, p < 0.01). There was a greater decrease in uncertainty among caregivers in the GA group than those in the usual care group (b = -0.46, p = 0.02). For both patients and caregivers, their past uncertainty was a significant predictor of their own current uncertainty (i.e., actor effect, p < 0.01). The individual's past uncertainty was a significant predictor of the other dyad member's current uncertainty (i.e., partner effect, p < 0.05), indicating an interdependent relationship between patient and caregiver uncertainty over time. CONCLUSIONS: Findings suggest patient and caregiver function as a unit with uncertainty levels affecting each other. Future interventions could build on GA to address uncertainty for older patients with advanced cancer and caregivers.

Life expectancy in older adults with advanced cancer: Evaluation of a geriatric assessment-based prognostic model.

OBJECTIVES: Oncologists estimate patients' prognosis to guide care. Evidence suggests oncologists tend to overestimate life expectancy, which can lead to care with questionable benefits. Information obtained from geriatric assessment may improve prognostication for older adults. In this study, we created a geriatric assessment-based prognostic model for older adults with advanced cancer and compared its performance to alternative models. MATERIALS AND METHODS: We conducted a secondary analysis of a trial (URCC 13070; PI: Mohile) capturing geriatric assessment and vital status up to one year for adults age ≥ 70 years with advanced cancer. Oncologists estimated life expectancy as 0-6 months, 7-12 months, and > 1 year. Three statistical models were developed: (1) a model including age, sex, cancer type, and stage (basic model), (2) basic model + Karnofsky Performance Status (≤50, 60-70, and 80+) (KPS model), and (3) basic model +16 binary indicators of geriatric assessment impairments (GA model). Cox regression was used to model one-year survival; c-indices and time-dependent c-statistics assessed model discrimination and stratified survival curves assessed model calibration. RESULTS: We included 484 participants; mean age was 75; 48% had gastrointestinal or lung cancer. Overall, 43% of patients died within one year. Oncologists classified prognosis accurately for 55% of patients, overestimated for 35%, and underestimated for 10%. C-indices were 0.61 (basic model), 0.62 (KPS model), and 0.63 (GA model). The GA model was well-calibrated. CONCLUSIONS: The GA model showed moderate discrimination for survival, similar to alternative models, but calibration was improved. Further research is needed to optimize geriatric assessment-based prognostic models for use in older adults with advanced cancer.

PA- and NP-led Ommaya clinics to manage leptomeningeal carcinomatosis.

OBJECTIVES: Physician assistants (PAs) and NPs are essential to quality care delivery. The need to demonstrate value and optimize PA and NP roles in neurology subspecialty clinics is unmet. We outline the development of a PA- and NP-led neuro-oncology procedural clinic and provide metrics to support the institutional and clinician value added. METHODS: We designed a PA- and NP-led Geisinger Ommaya Clinic (GOC) to manage leptomeningeal carcinomatosis (LMC) with defined clinician roles and the GOC treatment protocol. A retrospective review of 135 patients (2012-2019) compared survival outcomes for patients treated on the protocol compared with those treated off the protocol. RESULTS: Centralized care in the GOCs minimized shared physician encounters and improved PA and NP autonomy and utility. LMC therapy as part of the GOC protocol improved care continuity and survival outcomes. CONCLUSIONS: PA- and NP-led procedural clinics optimize use of these clinicians and open physician availability for nonprocedural duties. This research highlights the institutional patient and financial benefit while demonstrating the operational and leadership growth potential for PAs and NPs.

Implementation of Risk-reducing Strategies for Breast Cancer is Long Overdue.

Despite strong evidence that it is efficacious, chemoprevention has been underused in eligible women. Reasons offered not to adopt and initiate strategies to reduce the risk of breast cancer include the fear of adverse effects, medication costs, lack of reasonably accurate and feasible methods for assessing an individual's personal risk, and lack of established risk thresholds that maximize benefit and minimize harms. The article by Macdonald and colleagues remind us that the problem of lack of uptake of risk-reducing medications for breast cancer remains a worldwide clinical challenge despite endorsements from national and international organizations that recommend the use of risk-reducing medications for breast cancer with level I evidence. Several strategies are suggested to improve uptake and utilization of safe and effective chemoprevention medications with high therapeutic indices.See related article by Macdonald et al., p. 131.

Breast cancer risk reduction: Notable achievements and remaining challenges.

Millions of women in the United States are at increased risk of breast cancer. Multiple prospective, randomized clinical trials have demonstrated both the efficacy and safety of selective estrogen receptor modulators and aromatase inhibitors in reducing substantially the risk of invasive breast cancer in women at increased risk. Published tables are available to aid clinicians in shared decision-making regarding drug interventions with their patients who are at increased risk of breast cancer. Both professional and governmental agencies have advised that these interventions should be offered to women at increased risk of breast cancer. Doing so would reduce breast cancer morbidity substantially.

Relationships of self-perceived age with geriatric assessment domains in older adults with cancer.

OBJECTIVES: Older self-perceived age is associated with poor health and higher healthcare utilization in the geriatric population. We evaluated the associations of self-perceived age with geriatric assessment (GA) domain impairments in older adults with cancer. METHODS: This was a secondary analysis of baseline data from a GA cluster-randomized trial (URCC 13070; PI: Mohile). We included patients aged ≥70 with incurable stage III/IV solid tumor or lymphoma considering or receiving treatment and had ≥1 GA domain impairment other than polypharmacy. Multivariate analyses were used to evaluate the associations of age difference between chronological and self-perceived age (categorized into "feeling younger than chronological age" vs. "feeling the same or older than their chronological age") with GA domain impairments. RESULTS: We included 533 patients; mean age was 76.6 (SD 5.2). On multivariate analyses, compared to those who felt younger than their chronological age, those who felt the same or older were more likely to have impairments in physical performance [Adjusted Odds Ratio (AOR) 5.42, 95% Confidence Interval (CI) 1.69-17.40)], functional status (AOR 2.31, 95% CI 1.73-3.07), comorbidity (AOR 1.62, 95% CI 1.20-2.19), psychological health (AOR 2.62, 95% CI 1.85-3.73), and nutrition (AOR 1.65, 95% CI 1.20-2.28). They were also more likely to screen positively for polypharmacy (AOR 1.86, 95% CI 1.30-2.65). CONCLUSIONS: Older adults with cancer who felt the same or older than their chronological age were more likely to have GA domain impairments. Further studies are needed to better understand the relationships between self-perceived age, aging-related conditions, and outcomes in this population.

Exome Sequencing-Based Screening for BRCA1/2 Expected Pathogenic Variants Among Adult Biobank Participants.

Importance: Detection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. Objectives: To identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants. Design, Setting, and Participants: This is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2. Main Outcomes: Prevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers. Results: Of the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P < .001). Ovarian cancer history was present in 15 (10.1%) of 148 variant carriers and in 195 (0.6%) of 29 880 variant noncarriers (OR, 18.30; 95% CI, 10.48-31.4; P < .001). Among 89 BRCA1/2 carriers without prior testing but with comprehensive personal and family history data, 44 (49.4%) did not meet published guidelines for clinical testing. Conclusions and Relevance: This study found that compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with P/LP BRCA1/2 variants. These findings suggest that genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remain undetected within health care systems and may provide opportunities to reduce morbidity and mortality in patients.

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants.

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.

The Burdens and Uncertainties of Doing What One Should Do.

Despite FDA approval of drugs to reduce the risk of breast cancer in women at increased risk, uptake of these drugs has been poor despite the publication of numerous studies that demonstrate both their effectives and safety. National organizations have made recommendations for their use, but both physicians and their patients do not fully understand either breast cancer risk factors or risk assessment or the indications for using risk-reducing agents. Histologically predisposing conditions, such as ductal or lobular atypia and lobular carcinoma in situ, impart particularly high risks of developing subsequent invasive breast cancer. Resources should be committed to both provider and patient education to reduce the risk of breast cancer in women who are at increased risk. Cancer Prev Res; 10(8); 431-3. ©2017 AACR.

Ongoing data from the breast cancer prevention trials: opportunity for breast cancer risk reduction.

Selective estrogen receptor modulators (SERMs) reduce the risk of recurrence of invasive breast cancer and the incidence of first breast cancers in women who are at increased risk. Multiple, randomized clinical trials have shown both the efficacy and safety of SERMs in reducing the risk of breast cancer. Long-term follow-up as long as 20 years in the randomized trials shows persistent efficacy with acceptable safety. Hormone replacement therapy given concurrently with tamoxifen abrogates its preventive effect, but women with atypical hyperplasia derive particular benefit from SERM therapy. Aromatase inhibitors also reduce the risk of developing invasive breast cancer, but the experience with them for risk reduction is limited to few trials. National organizations have made recommendations to use SERMs and aromatase inhibitors to reduce the risk of breast cancer in high-risk women and additional efforts should be made to increase their use in clinical practice, where the number of women needed to treat to prevent one case of breast cancer conforms to accepted standards of preventive medicine.

Role of hormones in cancer prevention.

Risk for breast cancer can be easily and rapidly assessed using validated, quantitative models. Multiple randomized studies show that the selective estrogen response modifiers (SERMs) tamoxifen and raloxifene can safely reduce the risk of invasive breast cancer in both pre- and postmenopausal women. Treatment resulted in a 38% reduction in breast cancer incidence, and 42 women would need to be treated to prevent one breast cancer event in the first 10 years of follow-up. Reduction was larger in the first 5 years of follow-up than in years 5 to 10, but no studies treated patients for longer than 5 years. Thromboembolic events were significantly increased with all SERMs, whereas vertebral fractures were reduced. Tamoxifen provides net benefit to all premenopausal women who are at increased risk, whereas raloxifene reduces risk nearly as much in postmenopausal women and offers increased safety. Both tamoxifen and raloxifene reduce the incidence of in situ cancers. Lasofoxifene reduced the risk of breast cancer by 79% in postmenopausal women with osteoporosis. The MAP3 trial showed a 65% reduction in the annual incidence of invasive breast cancer in postmenopausal women who were at moderately increased risk for breast cancer who took the aromatase inhibitor exemestane. The IBIS-II trial showed a 53% reduction in the risk of invasive breast cancer in postmenopausal women aged 40 to 70 who took the aromatase inhibitor anastrozole. Of the 50 million white women in the United States aged 35 to 79, 2.4 million would have a positive benefit/risk index for chemoprevention.

Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline.

PURPOSE: To update the 2009 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS: A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and Cochrane Collaboration Library. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. Guideline recommendations were revised based on an Update Committee's review of the literature. RESULTS: Nineteen articles met the selection criteria. Six chemoprevention agents were identified: tamoxifen, raloxifene, arzoxifene, lasofoxifene, exemestane, and anastrozole. RECOMMENDATIONS: In women at increased risk of BC age ≥ 35 years, tamoxifen (20 mg per day for 5 years) should be discussed as an option to reduce the risk of estrogen receptor (ER) -positive BC. In postmenopausal women, raloxifene (60 mg per day for 5 years) and exemestane (25 mg per day for 5 years) should also be discussed as options for BC risk reduction. Those at increased BC risk are defined as individuals with a 5-year projected absolute risk of BC ≥ 1.66% (based on the National Cancer Institute BC Risk Assessment Tool or an equivalent measure) or women diagnosed with lobular carcinoma in situ. Use of other selective ER modulators or other aromatase inhibitors to lower BC risk is not recommended outside of a clinical trial. Health care providers are encouraged to discuss the option of chemoprevention among women at increased BC risk. The discussion should include the specific risks and benefits associated with each chemopreventive agent.

Selective estrogen receptor modulators and pharmacogenomic variation in ZNF423 regulation of BRCA1 expression: individualized breast cancer prevention.

The selective estrogen receptor modulators (SERM) tamoxifen and raloxifene can reduce the occurrence of breast cancer in high-risk women by 50%, but this U.S. Food and Drug Administration-approved prevention therapy is not often used. We attempted to identify genetic factors that contribute to variation in SERM breast cancer prevention, using DNA from the NSABP P-1 and P-2 breast cancer prevention trials. An initial discovery genome-wide association study identified common single-nucleotide polymorphisms (SNP) in or near the ZNF423 and CTSO genes that were associated with breast cancer risk during SERM therapy. We then showed that both ZNF423 and CTSO participated in the estrogen-dependent induction of BRCA1 expression, in both cases with SNP-dependent variation in induction. ZNF423 appeared to be an estrogen-inducible BRCA1 transcription factor. The OR for differences in breast cancer risk during SERM therapy for subjects homozygous for both protective or both risk alleles for ZNF423 and CTSO was 5.71.

Erythrocyte omega-6 and omega-3 fatty acids and mammographic breast density.

Diets low in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high in omega-3 (n-3) PUFAs may protect against breast cancer development. Associations of PUFA intake with mammographic density, an intermediate marker of breast cancer risk, have been inconsistent; however, prior studies have relied on self-reported dietary PUFA intake. We examined the association between circulating erythrocyte n-6 and n-3 PUFAs with mammographic density in 248 postmenopausal women who were not taking exogenous hormones. PUFAs in erythrocytes were measured by gas-liquid chromatography, and mammographic density was assessed quantitatively by planimetry. Spearman's correlation coefficients and generalized linear models were used to evaluate the relationships between PUFA measures and mammographic density. None of the erythrocyte n-6 or n-3 PUFA measures were associated with percent density or dense breast area.

Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data.

BACKGROUND: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and their ratio (2:16α-OHE1) in relation to breast cancer risk. METHODS: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.
 RESULTS: Higher premenopausal 2:16α-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16α-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). CONCLUSIONS: Premenopausal urinary 2:16α-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16α-OHE1 overall, although obesity may modify associations with 2-OHE1.

Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update.

PURPOSE: To provide recommendations on the follow-up and management of patients with breast cancer who have completed primary therapy with curative intent. METHODS: To update the 2006 guideline of the American Society of Clinical Oncology (ASCO), a systematic review of the literature published from March 2006 through March 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the recommendations were in need of updating. RESULTS: There were 14 new publications that met inclusion criteria: nine systematic reviews (three included meta-analyses) and five randomized controlled trials. After its review and analysis of the evidence, the Update Committee concluded that no revisions to the existing ASCO recommendations were warranted. RECOMMENDATIONS: Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of complete blood counts, chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic ultrasounds, computed tomography scans, [(18)F]fluorodeoxyglucose-positron emission tomography scans, magnetic resonance imaging, and/or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.