Ovarian Cancer Risk-Reduction and Screening in BRCA1/2 Mutation Carriers.

Objective: To determine the utilization of risk-reducing strategies and screening protocols for ovarian cancer in female BRCA1/2 carriers. Methods: This study was a sub-analysis of female participants from a larger multicenter, cross-sectional survey of BRCA1/2 mutation carriers unaffected by cancer. The questionnaire was administered electronically via email at four institutions located in the northeast United States. Data were analyzed with Fisher's exact test. Results: The survey was completed by 104 female BRCA mutation carriers. BRCA subtypes included 54.3% BRCA2, 41.0% BRCA1, and 2.9% both. The age at which patients underwent genetic testing varied 21.2% were 18-24 years, 25.0% were 25-34 years, 29.8% were 35-44 years, and 24.0% were 45 years or older. Nearly, all respondents (97.1%) reported that a provider had discussed risk-reducing surgeries. Of the 79 females who underwent genetic testing before 45 years of age, 53.2% reported that a health care provider recommended taking combined oral contraceptive pills (COCs) to reduce their risk of ovarian cancer, and, of these women, 88.1% chose to use them. COCs were offered at higher rates among women who were younger at the age of genetic testing (18-24: 86%, 25-34: 62%, 35-44: 23%; p < 0.0001). Approximately half (55.8%) of the respondents reported having been offered increased screening for possible early detection of ovarian cancer, of which 81.0% chose to undergo screening. The majority utilized a combination of transvaginal ultrasound and serum CA125 measurements. There were no differences observed in screening utilization based on BRCA mutation type. Conclusion: In our cohort of female BRCA mutation carriers, risk-reducing surgery was offered to almost all women, whereas only half were offered risk-reducing medication and/or increased screening. Further investigation is needed to identify barriers to the utilization of risk-reducing strategies among this high-risk population.

More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome.

Aging is a leading risk factor for cancer. While it is proposed that age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. We show that aging and cancer share a common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro and tested on clinical tissues. This signature, termed CellDRIFT, increased with age across multiple tissues, distinguished tumor from normal tissue, was escalated in normal breast tissue from cancer patients, and was transiently reset upon reprogramming. In addition, within-person tissue differences were correlated with predicted lifetime tissue-specific stem cell divisions and tissue-specific cancer risk. Our findings suggest that age-related replication may drive epigenetic changes in cells and could push them toward a more tumorigenic state.

The Utility of ctDNA in Lung Cancer Clinical Research and Practice: A Systematic Review and Meta-Analysis of Clinical Studies.

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.

Barriers to hormone therapy following prophylactic bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers.

OBJECTIVE: This study aimed to identify barriers to hormone therapy (HT) use among women with BRCA1/2 mutations after prophylactic bilateral salpingo-oophorectomy (BSO). METHODS: A cross-sectional, electronic survey was conducted of BRCA1/2 mutation carriers at Women and Infants Hospital, Yale Medical Center, Hartford Healthcare, and Maine Medical Center. This study was a subanalysis of a subset of female BRCA1/2 mutation carriers who had undergone a prophylactic BSO. Data were analyzed using the Fisher's exact test or t test. RESULTS: We performed a subanalysis of 60 BRCA mutation carriers who underwent a prophylactic BSO. Only 24 women (40%) reported ever using HT. HT use was higher in women who underwent their prophylactic BSO at age younger than 45 years (51% vs. 25%, P = 0.06). Among all women who had a prophylactic BSO, the majority (73%) reported that a provider talked to them about using HT. Two thirds reported having seen contradictory information in the media about long-term consequences of HT. Seventy percent listed their provider as the primary influence in their decision to start HT. The most common reasons for not starting HT included it not being recommended by their physician (46%) and that it was not necessary (37%). CONCLUSIONS: BRCA mutation carriers frequently undergo prophylactic BSO at young ages, and less than half report using HT. This study highlights barriers to HT use, such as patient fears and physician discouragement, and identifies potential areas to improve educational efforts.

The Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients.

BACKGROUND: Black cohosh (BC) (Cimicifuga racemosa) may prevent and treat breast cancer through anti-proliferative, pro-apoptotic, anti-estrogenic, and anti-inflammatory effects. This study sought to evaluate the effect of BC on tumor cellular proliferation, measured by Ki67 expression, in a pre-operative window trial of ductal carcinoma in situ (DCIS) patients. METHODS: Patients were treated pre-operatively for 2 to 6 weeks with BC extract. Eligible subjects were those who had DCIS on core biopsy. Ki67 was measured using automated quantitative immunofluorescence (AQUA) pre/post-operatively. Ki67, tumor volume, and hormone changes were assessed with 2-sided Wilcoxon signed-rank tests, α = .05. RESULTS: Thirty-one patients were treated for an average of 24.5 days (median 25; range 15-36). Ki67 decreased non-significantly (n = 26; P = .20; median pre-treatment 1280, post-treatment 859; range pre-treatment 175-7438, post-treatment 162-3370). Tumor volume, estradiol, and FSH did not change significantly. No grade 3 or 4 adverse events were reported. CONCLUSIONS: BC use showed no significant impact on cellular proliferation, tumor volume, or invasive disease upgrade rates in DCIS patients. It was well-tolerated, with no observed significant toxicities. Further study is needed to elucidate BC's role in breast cancer treatment and prevention.ClinicalTrials.gov Identifier: NCT01628536https://clinicaltrials.gov/ct2/show/NCT01628536.

A Case of Pheochromocytoma as a Subsequent Neoplasm in a Survivor of Childhood Embryonal Rhabdomyosarcoma.

Childhood cancer survivors are at risk for subsequent neoplasms. We describe the clinical presentation and genetic testing of a 29-year-old woman diagnosed with a pheochromocytoma 22 years post-treatment for childhood embryonal rhabdomyosarcoma of the bladder. Genetic testing for cancer predisposition revealed a pathogenic variant in BRCA2 and a variant of uncertain significance in MSH2. Pathogenic variants associated with deafness were also identified in GJB2. This article reports a novel subsequent neoplasm following childhood embryonal rhabdomyosarcoma, and discusses the potential contribution of genetic cancer predisposition to this case as well as the clinical implications of genetic testing.

Evidence of accelerated epigenetic aging of breast tissues in patients with breast cancer is driven by CpGs associated with polycomb-related genes.

PURPOSE: Age is one of the strongest risk factors for the development of breast cancer, however, the underlying etiology linking age and breast cancer remains unclear. We have previously observed links between epigenetic aging signatures in breast/tumor tissue and breast cancer risk/prevalence. However, these DNA methylation-based aging biomarkers capture diverse epigenetic phenomena and it is not known to what degree they relate to breast cancer risk, and/or progression. METHODS: Using six epigenetic clocks, we analyzed whether they distinguish normal breast tissue adjacent to tumor (cases) vs normal breast tissue from healthy controls (controls). RESULTS: The Levine (p = 0.0037) and Yang clocks (p = 0.023) showed significant epigenetic age acceleration in cases vs controls in breast tissue. We observed that much of the difference between cases and controls is driven by CpGs associated with polycomb-related genes. Thus, we developed a new score utilizing only CpGs associated with polycomb-related genes and demonstrated that it robustly captured epigenetic age acceleration in cases vs controls (p = 0.00012). Finally, we tested whether this same signal could be seen in peripheral blood. We observed no difference in cases vs. controls and no correlation between matched tissue/blood samples, suggesting that peripheral blood is not a good surrogate marker for epigenetic age acceleration. CONCLUSIONS: Moving forward, it will be critical for studies to elucidate whether epigenetic age acceleration in breast tissue precedes breast cancer diagnosis and whether methylation changes at CpGs associated with polycomb-related genes can be used to assess the risk of developing breast cancer among unaffected individuals.

Preventing Breast Cancer Through Identification and Pharmacologic Management of High-Risk Patients.

Breast cancer remains the most common cancer in women in the United States. For certain women at high risk for breast cancer, endocrine therapy (ET) can greatly decrease the risk. Tools such as the Breast Cancer Risk Assessment Tool (or Gail Model) and the International Breast Cancer Intervention Study risk calculator are available to help identify women at increased risk for breast cancer. Physician awareness of family history, reproductive and lifestyle factors, dense breast tissue, and history of benign proliferative breast disease are important when identifying high-risk women. The updated US Preventive Services Task Force and American Society of Clinical Oncology guidelines encourage primary care providers to identify at-risk women and offer risk-reducing medications. Among the various ETs, which include tamoxifen, raloxifene, anastrozole, and exemestane, tamoxifen is the only one available for premenopausal women aged 35 years and older. A shared decision-making process should be used to increase the usage of ET and must be individualized. This individualized approach must account for each woman's medical history and weigh the benefits and risks of ET in combination with the personal values of the patient.

Family planning in carriers of BRCA1 and BRCA2 pathogenic variants.

BRCA1 and BRCA2 pathogenic variant carriers have a high lifetime risk of developing breast and ovarian malignancies. Given the risks and significant ramifications of undergoing risk-reducing surgeries, many pathogenic variant carriers unaffected by cancer (previvors) struggle with family planning and reproductive decision making. The objective of this study was to determine the attitudes and practices of BRCA1 and BRCA2 pathogenic variant carriers with respect to family planning decision making. A cross-sectional survey was conducted of BRCA1 and BRCA2 previvors at four Northeastern medical centers. The survey was administered electronically via email using REDCap. The survey included demographic information as well as questions about genetic testing, prophylactic surgeries, family planning, and partnering. Data were analyzed with Fisher's exact tests and t tests. The survey was completed by 139 of 422 BRCA1 and BRCA2 pathogenic variant carriers (response rate 33%). Thirteen were excluded from analysis due to self-reported cancer history. Of the remaining 126, 21 (16.7%) were male and 105 (83.3%) were female. Female participants <35 years old at the time of genetic testing were significantly more likely than those 35 or greater to report feeling urgency to have a family after finding out about their BRCA1 and BRCA2 pathogenic variant (p < 0.0001). Younger women also reported their genetic status had a stronger impact on their romantic relationships (p = 0.029). Men were significantly more likely to report that they felt no urgency to have a family compared to women (p < 0.0001). Our study reflects the complex decision making for previvors and the intricacies of family planning in this population. Providers can use this knowledge as a guide to counsel patients about reproductive options.

Should You Recommend Direct-to-Consumer Genetic Testing for This Patient? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

In recent years, the number of patients choosing to have direct-to-consumer (DTC) genetic testing without involving their clinicians has increased substantially. For example, the number of subscribers to a commonly used testing site has grown to more than 10 million. These services have been heavily marketed in the United States and often include information about ancestry; genetic traits; and, increasingly, disease risk. In clinical care, genetic testing by a physician is accompanied by both pre- and posttest counseling by a trained genetic counselor. However, there are not enough genetic counselors to meet the needs of all persons contemplating DTC genetic testing. Formal genetic counseling includes preparation of a family pedigree; a discussion about potential benefits, the possibility that some information might be stressful to receive or difficult to understand, and the potential for disclosure of genetic information; and a detailed informed consent process. Some DTC tests for genetic susceptibilities look for only a few known mutations in a particular gene (such as BRCA1); a negative test result does not exclude the possibility of a clinically important mutation. A positive DTC genetic test result that might change clinical management should be followed by a confirmatory test through a genetics laboratory. Here, 2 expert physicians-a general internist and a medical oncologist with genetics experience-discuss an approach to counseling a patient who is considering DTC testing to learn more about his ancestry and his risk for metabolic syndrome.

Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline.

PURPOSE: To develop recommendations for management of patients with breast cancer (BC) with germline mutations in BC susceptibility genes. METHODS: The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an Expert Panel to develop recommendations based on a systematic review of the literature and a formal consensus process. RESULTS: Fifty-eight articles met eligibility criteria and formed the evidentiary basis for the local therapy recommendations; six randomized controlled trials of systemic therapy met eligibility criteria. RECOMMENDATIONS: Patients with newly diagnosed BC and BRCA1/2 mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in BRCA1/2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in BRCA1/2 carriers. Radiation therapy should not be withheld in ATM carriers. For patients with germline TP53 mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in BRCA carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1/2 carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines.

TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).

PURPOSE: Platinum compounds have activity in triple-negative breast cancer (TNBC) in germline BRCA mutation carriers (BRCA carriers). Limited data exist for estrogen receptor (ER)-positive (+) breast cancer among BRCA carriers. INFORM is a randomized, multicenter, phase II trial comparing pathologic complete response (pCR) rates (ypT0/is, N0) after neoadjuvant single-agent cisplatin (CDDP) versus doxorubicin-cyclophosphamide (AC) in BRCA carriers with stage I-III human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Secondary objectives included residual cancer burden scores (RCB) of 0 or 1 (combined) and toxicity. The goal was to determine whether pCR was ≥ 20% higher with CDDP than AC. PATIENTS AND METHODS: BRCA carriers with cT1-3 (≥ 1.5 cm), cN0-3 HER2-negative breast cancer were randomly assigned to preoperative CDDP (75 mg/m2 every 3 weeks × 4 doses) or AC (doxorubicin 60 mg/m2; cyclophosphamide 600 mg/m2 every 2-3 weeks × 4 doses) followed by surgery. Pathologic responses were confirmed by central review. RESULTS: A total of 118 patients were randomly assigned; 117 were included in outcome analyses. Mean age was 42 years (range, 24-73 years); 69% were BRCA1+, 30% were BRCA2+, and 2% had both mutations. Clinical stage was I for 19%, II for 63%, and III for 18%; 45% had nodal involvement at baseline. Seventy percent had TNBC. Clinical and tumor characteristics were well matched between treatment arms. The pCR rate was 18% with CDDP and 26% with AC, yielding a risk ratio (RR) of 0.70 (90% CI, 0.39 to 1.2). The risk of RCB 0 or 1 (RCB 0/1) was 33% with CDDP and 46% with AC (RR, 0.73; 90% CI, 0.50 to 1.1). Both regimens were generally well tolerated without unexpected toxicities. CONCLUSION: pCR or RCB 0/1 is not significantly higher with CDDP than with AC in BRCA carriers with stage I-III HER2-negative breast cancer for both TNBC and ER+/HER2-negative disease.

Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update.

PURPOSE: To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction. METHODS: An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS: A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update. UPDATED RECOMMENDATIONS: In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines.

The impact of communication style on patient satisfaction.

BACKGROUND: Communication between patients and health providers influences patient satisfaction, but it is unknown whether similarity in communication styles results in higher patient satisfaction. METHODS: This study was conducted in the Smilow Cancer Hospital Breast Center. During routine follow-up visits, patients completed a Communication Styles Assessment (CSA), health survey (SF-12), Princess Margaret Hospital Satisfaction with Doctor Questionnaire, and brief demographic form. Physicians and Advanced Practice Providers were also asked to complete the CSA. Patients and providers were blinded to each other's responses. A communication styles concordance score was calculated as the Pearson correlation between 80 binary CSA items for each provider/patient pair. Factors affecting patient satisfaction scores were assessed in mixed-effects models. RESULTS: In total, 330 patients were invited to participate; of these 289 enrolled and 245 returned surveys. One hundred seventy-four completed all survey components, and 18 providers completed the CSA. Among the factors considered, physical health score (effect size = 0.0058, 95% CI 0.00051 to 0.0011, p = 0.032) and employment status (0.12, 95% CI - 0.0094 to 0.25, p = 0.069) had the greatest impact on patient satisfaction. However, patients who were not employed and less physically healthy had significantly elevated satisfaction scores when their communication style was more similar to their provider's (1.52, 95% CI 0.66 to 2.38, p = 0.0016). CONCLUSIONS: Patients who were physically healthy and employed were generally more satisfied with their care. The similarity in communication styles of patients and providers had a greater impact on patient satisfaction for patients who were less physically healthy and not employed.

Increased epigenetic age in normal breast tissue from luminal breast cancer patients.

BACKGROUND: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. RESULTS: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). CONCLUSIONS: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

Genetic testing for hereditary prostate cancer: Current status and limitations.

A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM). Currently, there are no uniform guidelines on the definition of hereditary prostate cancer and genetic testing. With the advent of next-generation sequencing, which is capable of testing multiple genes simultaneously, and the approval of olaparib for BRCA1/BRCA2 or ATM-mutated, metastatic, castrate-resistant prostate cancer, it is being recognized that the results of genetic testing have an impact on therapeutic strategies. In this review, the authors examine the role of genetic counseling and testing, the challenges of insurance coverage for testing, the available germline and somatic testing panels, and the complexity of each testing method and its implications. Cancer 2018. © 2018 American Cancer Society.

Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I-III HER2-positive breast cancer.

PURPOSE: The purpose of this two-cohort Phase II trial was to estimate the pathologic complete response (pCR: ypT0/is ypN0) rate when trastuzumab plus pertuzumab are administered concurrently during both the taxane and anthracycline phases of paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) neoadjuvant chemotherapy. METHODS: The pCR rates were assessed separately in hormone receptor (HR) positive and negative cases following Simon's two-stage design, aiming to detect a 20% absolute improvement in pCR rates from 50 to 70 and 70 to 90% in the HR-positive and HR-`negative cohorts, respectively. RESULTS: The HR-negative cohort completed full accrual of 26 patients; pCR rate was 80% (95% CI 60-91%). The HR+ cohort was closed early after 24 patients due to lower than expected pCR rate of 26% (95% CI 13-46%) at interim analysis. Overall, 44% of patients (n = 22/50) experienced grade 3/4 adverse events. The most common were neutropenia (n = 10) and diarrhea (n = 7). There was no symptomatic heart failure, but 28% (n = 14) had ≥ 10% asymptomatic decrease in LVEF; in one patient, LVEF decreased to < 50%. Cardiac functions returned to baseline by the next assessment in 57% (8/14) of cases. CONCLUSIONS: Eighty percent of HR-negative, HER2-positive breast cancers achieve pCR with paclitaxel/FEC neoadjuvant chemotherapy administered concomitantly with pertuzumab and trastuzumab. These results are similar to pCR rates seen in trials using HER2-targeted therapy during the taxane phase only of sequential taxane-anthracycline regimens and suggest that we have reached a therapeutic plateau with HER2-targeted therapies combined with chemotherapy in the neoadjuvant setting.

Impacts of Early Guideline-Directed 21-Gene Recurrence Score Testing on Adjuvant Therapy Decision Making.

PURPOSE: The 21-gene recurrence score (RS) assay is used to help formulate adjuvant chemotherapy recommendations for patients with estrogen receptor-positive, early-stage breast cancer. Most frequently, medical oncologists order RS after surgery. Results take an additional 2 weeks to return, which can delay decision making. We conducted a prospective quality-improvement project to assess the impact of early guideline-directed RS ordering by surgeons before the first visit with a medical oncologist on adjuvant therapy decision making. MATERIALS AND METHODS: Surgical oncologists ordered RS testing following National Comprehensive Cancer Network guidelines at time of diagnosis or at time of surgery between July 1, 2015 and December 31, 2015. We measured the testing rate of patients eligible for RS, time to chemotherapy decisions, rates of chemotherapy use, accrual to RS-based clinical trials, cost, and physician acceptance of the policy and compared the results to patients who met eligibility criteria for early guideline-directed testing during the 6 months before the project. RESULTS: Ninety patients met eligibility criteria during the testing period. RS was ordered for 91% of patients in the early testing group compared with 76% of historical controls ( P < .001). Median time to chemotherapy decision was significantly shorter in the early testing group (20 days; 95% CI, 17 to 23 days) compared with historical controls (32 days; 95% CI, 29 to 35 days; P < .001). There were no significant differences in time to chemotherapy initiation, chemotherapy use, RS-based trial enrollment, or calculated costs between the groups. CONCLUSION: Early guideline-directed RS testing in selected patients is an effective way to shorten time to treatment decisions.

Does lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer?

BACKGROUND: Women ≥70 years old with clinically (c) lymph node (LN) negative (-), hormone receptor (HR) positive (+) breast cancer are recommended not to be routinely staged with a sentinel LN biopsy. We sought to determine how this affects adjuvant decision-making. METHODS: Statistical analyses were performed to determine the association of LN evaluation with adjuvant chemotherapy and radiation therapy in cLN-, HR + breast cancer patients in the National Cancer Database. RESULTS: Between 2004 and 2013, there were 193,728 patients aged 70-90 with cLN-, HR + breast cancer; 15.0% were LN+. LN + patients were more likely to receive chemotherapy (28.3% vs. 5.5%, p < 0.001), hormonal therapy (83.6% vs. 71.4%, p < 0.001), post-lumpectomy radiation therapy (81.4% vs. 73.6%, p < 0.001) and post-mastectomy radiation therapy (30.3% vs. 5.1%, p < 0.001). CONCLUSION: 15% of patients aged 70-90 will be LN+. These patients more frequently receive systemic and radiation therapy. LN status may affect treatment in these patients.