: According to the American Cancer Society, there are currently 2 million breast cancer (BC) survivors in the USA and 20% of them cope with lymphedema (LE). The primary aim of this study was to ...determine the predictive factors of BC‐related LE. The secondary aim was to investigate the impact of predictors on the severity of LE. The study design was intended to be a 1:2 matched case–control study. Instead, we stratified on age (±10 years), radiation therapy (y/n), and type of operation (SM/MRM/MRM with tram). Patients who underwent BC surgery between 1990 and 2000 at UPMC Magee‐Womens Hospital were reviewed for LE. Data were collected on 52 women with LE and 104 female controls. Logistic regression was utilized to assess the relationship between risk factors and LE. Ordinal logistic regression was performed to determine the association between risk factors and severity of LE. Severity was defined according to the volume difference between affected and unaffected limbs. Risk factors considered were occupation/hobby (hand use), TNM stage, number of dissected nodes, number of positive nodes, tumor size, infection, allergy, diabetes mellitus, hypertension, hypothyroidism, chronic obstructive pulmonary disease, and body mass index (BMI). LE was mild in 43 patients and was moderate/severe in nine patients. The level of hand use in the control group was categorized as low in 56 (54%), medium in 15 (14%), and high in 33 (32%) patients. The corresponding frequencies were 14 (33%), 6 (14%) and 23 (53%) for patients with mild LE and 3 (33%), 1 (11%), 5 (56%) for patients with moderate/severe LE (p < 0.05). Infection of the operated side arm was reported by two (2%) patients in the control group, 14 (33%) patients with mild LE and five (56%) patients with moderate/severe LE (p < 0.05). The mean BMI was 26.1 kg/m2 (SD 4.9) for the control group, 29.0 kg/m2 (SD 5.9) for the mild LE group and 30.9 kg/m2 (SD 7.5) for patients with moderate/severe LE (p < 0.05). The results of this stratified case–control study demonstrated that the risk and severity of LE was statistically related to infection, BMI, and level of hand use.
: Selective estrogen receptor modulators (SERMs) are used for the treatment of invasive breast cancer. Chemoprevention is the use of specific natural or synthetic chemical agents to reverse, ...suppress, or prevent the progression of premalignant lesions to invasive carcinoma. The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to its use in breast cancer prevention. Four large trials have used tamoxifen, the prototypical SERM, as a breast cancer chemopreventive agent with differing results. In the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the risk of invasive breast cancer by 49%. Tamoxifen also reduced the incidence of benign breast disease as well as the number of breast biopsies in the treated women. Three other randomized prevention trials comparing tamoxifen with placebo have been reported and show a reduction in breast cancer incidence of 38%. Serum levels of estrone sulfate and testosterone are significantly associated with breast cancer risk, and estradiol appears to be more strongly associated with breast cancer in high‐risk women. Raloxifene is comparable to tamoxifen in its ability to reduce the risk of breast cancer in postmenopausal, high‐risk women and has fewer side effects, as shown in the study of tamoxifen and raloxifene. Several ongoing and planned studies will evaluate the ability of aromatase inhibitors to reduce the risk of breast cancer in women at increased risk.
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.
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.
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).
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.
Hormones have been implicated as modulators of cognitive functioning. For instance, results of our previous work in women with breast cancer showed that cognitive impairment was more severe and ...involved more memory domains in those who received adjuvant tamoxifen therapy compared with women who received chemotherapy alone or no adjuvant therapy. Recently aromatase inhibitors such as anastrozole have been used in lieu of tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor-positive, early-stage breast cancer. Plasma estrogen levels are significantly lower in women who receive anastrozole compared with those who receive tamoxifen. We hypothesized, therefore, that anastrozole would have a more profound effect on cognitive function than tamoxifen, a mixed estrogen agonist/antagonist.
To test this hypothesis we compared cognitive function in women with early-stage breast cancer who received tamoxifen with those who received anastrozole therapy in a cross-sectional study. We evaluated cognitive function, depression, anxiety, and fatigue in 31 postmenopausal women with early-stage breast cancer who were between the ages of 21 and 65 years and treated with tamoxifen or anastrozole for a minimum of 3 months.
The results showed that women who received anastrozole had poorer verbal and visual learning and memory than women who received tamoxifen.
Additional, prospective studies are needed to validate and confirm the changes in cognitive function associated with hormone therapy for breast cancer.
Controversy exists regarding the association between CYP2D6 enzyme activity and tamoxifen effectiveness in the adjuvant treatment of invasive breast cancer; however, this association in the primary ...prevention of breast cancer is unknown.
We conducted a nested case-control study in the context of the NSABP P1 and P2 prevention trials to determine the impact of CYP2D6 genotype, CYP2D6 inhibitor use, and metabolizer status (CYP2D6 genotype combined with CYP2D6 inhibitor use), on breast cancer events. Women who developed breast cancer (both noninvasive and invasive) while on 5 years of selective estrogen receptor modulators therapy (cases) were matched to controls free of breast cancer. Comprehensive CYP2D6 genotyping was conducted for alleles associated with absent (*3, *4, *5, and *6), reduced (*10, *17, and *41), and increased (*1XN and *2XN) enzyme activity. Information regarding the use of CYP2D6 inhibitors was recorded.
A total of 591 cases were matched to 1,126 controls and DNA was genotyped in more than 97%. In patients treated with tamoxifen, there was no association of CYP2D6 genotype OR (extensive/poor metabolizer): 0.90; 95% CI: 0.46-1.74, P = 0.74), use of a potent CYP2D6 inhibitor (OR 0.92; 95% CI: 0.575-1.486), or CYP2D6 metabolizer status (OR 1.03; 95% CI: 0.669-1.607) with breast cancer occurrence. Likewise, there was no association between any CYP2D6 metabolism parameter with breast cancer events in raloxifene-treated patients.
In the NSABP P1 and P2 clinical trials, alterations in CYP2D6 metabolism are not associated with either tamoxifen or raloxifene efficacy.
Objective: This study explored whether average urinary estrogen metabolites in breast cancer high-risk women can be used to identify a subgroup of women at particularly high risk to develop breast ...cancer, to which prevention strategies should be addressed. Methods: The population consisted of 77 high-risk women, 30 breast cancer patients and 41 controls. All subjects answered a standardized questionnaire; height and weight and spot urine samples were also obtained. Urine hydroxyestrogen metabolites were measured in triplicate by enzyme immunoassay, and the estrogen metabolite ratios for each individual were calculated. Results: The 2:16 OHE ratio (2-hydroxyestrone/16-alpha-hydroxyestrone) in women at high risk for breast cancer was similar to that observed in the breast cancer group (1.76 ± 2.33 versus 1.29 ± 0.80) and lower than in controls (2.47 ± 1.14; P = 0.00). At the multivariate linear regression model, the 2:16 OHE ratio was significantly associated with diagnosis (P = 0.000 for both the high risk and breast cancer group versus the controls) and body mass index (P = 0.005), but not with age (P = 0.604), or smoking history (P = 0.478). Conclusions: This study suggests that lower urinary 2:16 OHE ratios are predictors of breast cancer risk. Profiling estrogen metabolites may identify women who are more probably to develop breast cancer within a population of women with known risk factors and may help to further elucidate the clinical relevance of urinary 2:16 OHE ratios as clinical markers and prognostic indicators in this population.
Learning Objectives
After completing this course, the reader will be able to:
Identify the most important clinical genetic syndromes that increase the risk of hereditary breast cancer.
Describe ...surgical management options that reduce the risk of developing hereditary breast cancer.
Outline the risks and benefits of using chemopreventative interventions in carriers of genetic mutations that increase the risk of hereditary breast cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Clinicians should recognize the genetic syndromes that predispose to the development of breast cancer so that patients may be afforded the opportunity to have genetic testing to assist them and their family members in making medical management decisions. Approximately 80%–90% of hereditary breast cancer cases are caused by mutations in the BRCA1 and BRCA2 genes. Other important clinical genetic predispositions include Cowden syndrome, Li‐Fraumeni syndrome, Peutz‐Jeghers syndrome, and ataxia‐telangiectasia. The key to identifying women who are at risk for a hereditary breast cancer lies in obtaining an adequate, three‐generation family history, including ethnic background. For unaffected women, breast cancer risks can be estimated using the quantitative models of Gail and Claus, but there are limitations to these models. Other quantitative models predict the likelihood that a patient is carrying a mutated gene. Genetic testing is available at selected laboratories for each of the hereditary syndromes described, and there are three possible outcomes to testing. These outcomes and their management implications are described in detail. Clinical management options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic surgery. Application of these principles can reduce morbidity in women with genetic predispositions to breast cancer.
To determine an effective, evidence-based, postoperative surveillance strategy for the detection and treatment of recurrent breast cancer. Tests are recommended only if they have an impact on the ...outcomes specified by American Society of Clinical Oncology (ASCO) for clinical practice guidelines.
All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring.
Outcomes of interest include overall and disease-free survival, quality of life, toxicity reduction, and secondarily cost-effectiveness.
A search was performed to determine all relevant articles published over the past 20 years on the efficacy of surveillance testing for breast cancer recurrence. These publications comprised both retrospective and prospective studies.
Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design.
The possible consequences of false-positive and -negative tests were considered in evaluating a preference for one of two tests providing similar information. Cost alone was not a determining factor.
The attached guidelines and text summarize the updated recommendations of the ASCO breast cancer expert panel. Data are sufficient to recommend monthly breast self-examination, annual mammography of the preserved and contralateral breast, and a careful history and physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually. Data are not sufficient to recommend routine bone scans, chest radiographs, hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen CA 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans.
The recommendations of the breast cancer expert panel were evaluated and supported by the ASCO Health Services Research Committee reviewers and the ASCO Board of Directors.
PDF
