Juhee Song

High incidence of germline BRCA mutation in patients with ER low-positive/PR low-positive/HER-2 neu negative tumors.

The 2015 National Comprehensive Cancer Network guidelines recommend that genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple‐negative breast cancer (TNBC). As a result of the 2010 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast cancer, patients with breast cancers that are estrogen receptor (ER) or progesterone receptor (PR) low‐positive (1%‐9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low‐positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in undertesting for BRCA mutations.

BRCAPRO 6.0 Model Validation in Male Patients Presenting for BRCA Testing

BACKGROUND BRCAPRO is a risk assessment model to estimate the risk of carrying a BRCA mutation. BRCA mutation carriers are at higher risk of developing breast, ovarian, pancreatic, and prostate cancer. BRCAPRO was developed for women and found to be superior to other risk assessment models. The present study evaluated the validity of BRCAPRO at predicting the risk of male patients carrying a BRCA mutation. PATIENTS AND METHODS A total of 146 men who presented for genetic counseling and testing from February1997 to September 2011, and their test results were included in the present study. BRCAPRO risk assessment for all patients was calculated using the BRCAPRO clinical CancerGene assessment software. RESULTS The mean age at presentation was 57 years. Of the 146 patients, 48 had breast cancer, 18 had pancreatic cancer, 39 had prostate cancer, 27 had other primary cancers, and 37 had no cancer. Fifty patients (34%) tested positive for a BRCA mutation (22 BRCA1, 27 BRCA2, and 1 BRCA1 and BRCA2). The mean BRCAPRO score for all patients was 24.96%. The BRCAPRO score was significantly higher for patients who tested positive for a BRCA mutation (46.19% vs. 13.9%, p < .01). The area under the receiver operating characteristics curve was 0.83 for all patients for the BRCAPRO score to predict the risk of carrying a BRCA mutation. At a cutoff point of 30.02%, the sensitivity, specificity, positive predictive value, and negative predictive value were 0.74, 0.81, 0.67, and 0.86, respectively. CONCLUSION BRCAPRO appears to be a valid risk assessment tool for determining the risk of carrying a BRCA mutation in men. IMPLICATIONS FOR PRACTICE Men carrying genetic mutations in the BRCA gene have a greater risk than the general population of developing certain types of cancer, including breast, pancreatic, and prostate cancer. BRCAPRO is a risk assessment model that predicts the risk of carrying a BRCA mutation. The present study aimed at validating BRCAPRO for use with men seen for genetic counseling, whether affected by cancer or not. The data available for 146 patients revealed that BRCAPRO was effective at identifying patients at risk of BRCA mutation. These findings could help in identifying a subset of high-risk patients who should proceed to genetic testing.

Association between weight gain during adjuvant chemotherapy for early-stage breast cancer and survival outcomes

Obese and overweight women have an increased risk of breast cancer and worse outcomes at the time of diagnosis. Women tend to gain weight after breast cancer diagnosis and during chemotherapy for early‐stage disease, which may in turn increase risk for worse outcomes. We examined if weight gained during adjuvant chemotherapy was associated with worse survival outcomes. We queried our database for data on patients who received adjuvant third‐generation chemotherapy for early‐stage breast cancer. Univariate and multivariate analyses by Cox regression were performed for survival outcomes across three categories according to BMI variation from start to end of chemotherapy: >0.5 kg/m2 loss or gain and stable BMI (±0.5 kg/m2). We included 1998 patients in this study. Women over 50 years old and postmenopausal were more likely to lose weight during adjuvant chemotherapy, whereas women under 30 years old gained more weight (P < 0.001). At 1 year postchemotherapy, patients tended to return to their original weight (ρ = −0.3, P < 0.001). On multivariate analysis, BMI increase of >0.5 kg/m2 compared to maintaining BMI was marginally associated with increased locoregional recurrence risk (HR: 2.53; 95% CI, 1.18–5.45; P = 0.017), adjusting for grade, stage, and radiation delivery. Weight variation during adjuvant chemotherapy for early‐stage breast cancer may occur as both weight gain and weight loss in a balanced manner. Furthermore, this variation seems to be transient in nature and does not appear to significantly influence recurrence rates and overall survival.

Safety and Efficacy of Panitumumab Plus Neoadjuvant Chemotherapy in Patients With Primary HER2-Negative Inflammatory Breast Cancer

Importance Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC. Objective To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC. Design, Setting, and Participants Women with primary HER2-negative IBC were enrolled from 2010 to 2015 and received panitumumab plus neoadjuvant chemotherapy. Median follow-up time was 19.3 months. Tumor tissues collected before and after the first dose of panitumumab were subjected to immunohistochemical staining and RNA sequencing analysis to identify biomarkers predictive of pCR. Intervention Patients received 1 dose of panitumumab (2.5 mg/kg) followed by 4 cycles of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks. Main Outcomes and Measures The primary end point was pCR rate; the secondary end point was safety. The exploratory objective was to identify biomarkers predictive of pCR. Results Forty-seven patients were accrued; 7 were ineligible. The 40 enrolled women had a median age of 57 (range, 23-68) years; 29 (72%) were postmenopausal. Three patients did not complete therapy because of toxic effects (n = 2) or distant metastasis (n = 1). Nineteen patients had triple-negative and 21 had hormone receptor–positive IBC. The pCR and pCR rates were overall, 11 of 40 (28%; 95% CI, 15%-44%); triple-negative IBC, 8 of 19 (42%; 95% CI, 20%-66%); and hormone receptor–positive/HER2-negative IBC, 3 of 21 (14%; 95% CI, 3%-36%). During treatment with panitumumab, nab-paclitaxel, and carboplatin, 10 patients were hospitalized for treatment-related toxic effects, including 5 with neutropenia-related events. There were no treatment-related deaths. The most frequent nonhematologic adverse event was skin rash. Several potential predictors of pCR were identified, including pEGFR expression and COX-2 expression. Conclusions and Relevance This combination of panitumumab and chemotherapy showed the highest pCR rate ever reported in triple-negative IBC. A randomized phase 2 study is ongoing to determine the role of panitumumab in patients with triple-negative IBC and to further validate predictive biomarkers. Trial Registration ClinicalTrials.gov Identifier: NCT01036087

Prevalence of cognitive impairment in patients with hematologic cancers preceding stem cell transplantation: Program for healthy aging.

32 Background: Older adults, 65 years of age and older, with hematologic cancers may be at higher risk for cognitive impairment. It is postulated that the etiology of cognitive impairment in cancer may a combination of age-related and chemotherapy related cognitive impairment. METHODS We conducted a retrospective cohort analysis, of older adult patients 65 years and older evaluated at the Program for Healthy Aging at MD Anderson from January 1, 2013 through March 31, 2015. Cognitive assessment was evaluated through personal interview, and the Montreal cognitive assessment, functional assessment utilizing ADLs and IADLs. Screening for depression was conducted with the PHQ-9. Patients were interviewed regarding risk factors for dementia including depression, concussions, alcohol abuse, and family history of dementia. Level of education was assessed. Patients were euthymic. Cognitive impairment was defined as an abnormal MOCA without functional impairment, dementia was defined as an abnormal MOCA with functional impairment. Imaging and assessment for reversible factors of memory loss was conducted. SAS 9.4 (SAS Institute INC, Cary, NC) was used for data analysis. RESULTS The majority of these 62 patients had received chemotherapy for more than 2 years. Cognitive impairment and/or dementia were identified in 50 (80.6%) patients. Types of dementia included Alzheimers disease (n = 4, 8%), vascular dementia (n = 5, 10 %), and mixed dementia (n = 15, 30%).Mild cognitive impairment was evidenced in 14 cases (28%) The majority of cases of dementia with known stage were early stage dementia (n = 13, 72.2%), moderate stage dementia (n = 3, 16.7%), and advanced or severe dementia (n = 2, 11.1%). Brain imaging was performed identifying white matter microischemic changes, cerebrovascular accidents and brain atrophy in some cases. No significant thyroid abnormalities, B12 deficiency or other reversible causes were identified. CONCLUSIONS Cognitive impairment and dementia are prevalent in older patients with hematologic malignancies. Identification and management of this condition may prevent delirium and hospital complications during stem cell transplantation.

Overall survival in older patients with cancer

Objectives A growing number of patients with cancer are older adults. We sought to identify the predictors for overall survival (OS) in older adults with solid tumour and haematological malignancies between January 2013 and December 2016. Methods Retrospective cohort study. A comprehensive geriatric assessment was performed, with a median follow-up of 12.8 months. Analysis: univariate and multivariate Cox proportional hazards regression analysis. Results In this study, among the 455 patients with last follow-up date or date of death, 152 (33.4%) died during the follow-up. The median follow-up is 12.8 months (range 0.2–51.1 months) and the median OS is 20.5 months (range 0.3–44.5 months). Among all older patients with cancer, predictors of OS included male gender, cancer stage, malnutrition, history of smoking, heavy alcohol use, frailty, weight loss, major depression, low body weight and nursing home residence. Traditional performance scores (Eastern Cooperative Oncology Group (ECOG) and Karnofsky Performance Scale (KPS)) were predictors of OS. Independent predictors included age >85 years and haematological malignancies. Among solid tumours (n=311) in addition to the above predictors, comorbidity, gait speed and vitamin D deficiency were associated with OS. Conclusions We identified specific geriatric factors associated with OS in older patients with cancer, and comparable in predictive ability to traditional performance scores such as KPS and ECOG. Prospective studies will be necessary to confirm our findings.

Cognitive impairment and dementia in older cancer patients.

e269 Background: Chemotherapy effect on cognitive function has also been described in women with breast cancer. Our objective was to define the prevalence of cognitive impairment and dementia in older patients with cancer. METHODS This is a retrospective study at the Program for Healthy Aging at MD Anderson Cancer Center between January 1, 2013 and March 31, 2015. Patients with cancer, 65 years of age and older underwent functional and cognitive testing through personal interview, using IADLs, ADLs, and the Montreal cognitive assessment (MOCA). Screening for depression used PHQ-9. Risk factors for dementia assessed, included depression, concussions, alcohol abuse, and family history of dementia. Level of education was determined. Cognitive impairment was diagnosed with an abnormal MOCA ( < 26) without functional impairment, dementia was diagnosed with an abnormal MOCA with functional impairment. Imaging and assessment for reversible factors of memory loss was conducted. SAS 9.4 (SAS Institute INC, Cary, NC) was used for data analysis. RESULTS 192 patients were evaluated, male gender (n = 93, 48.4%), female (n = 99, 51.6%), mean age 78 years old (SD, 7) range 65 to 94 years. Sixty-two patients (32.3%) with a hematological malignancy; 26 (13.5%) with breast cancer; 22 (11.5%) with GI cancer; 19 (9.9%) with prostate malignancy; 16 (8.3%) with lung cancer; 14 (7.3%) with bladder cancer; and 33 (17.2%) with other malignancies. Cognitive impairment and/or dementia was identified in 118 (61.5%) patients. Mild cognitive impairment was evidenced in 27 cases (18.2%). Types of dementia included Alzheimers disease (n = 11, 7.4%), vascular dementia (n = 21, 14.2%), and mixed dementia (n = 59, 39.9%). The majority of cases of dementia were early stage dementia (n = 45, 56.3%), moderate stage dementia (n = 29, 36.3%), and advanced or severe dementia (n = 6, 7.5%). No significant thyroid abnormalities, B12 deficiency or other reversible causes were identified. CONCLUSIONS Cognitive impairment and/or dementia are commonly seen in patients with cancer in a comprehensive cancer center. Further research in this area is necessary.

Prevalence of low bone mass and osteoporosis in patients with cancer: Program for healthy aging.

30 Background: Older adults, 65 years of age and older, with cancer may be at higher risk for low bone mass or osteoporosis, however, the exact magnitude of this condition is unknown. It is postulated that the etiology of low bone mass and osteoporosis in cancer may be a combination of age-related and cancer therapy related bone loss. METHODS We conducted a retrospective cohort analysis, of older adult cancer patients evaluated at the Program for Healthy Aging at MD Anderson from January 1, 2013 through March 31, 2015. Bone mineral density (BMD) was assessed with a Hologic W densitometer, with a CV% of 1%. Information on prior fractures and falls were also collected. RESULTS One hundred and nine patients with Bone density tests were included in the analysis, with males (n = 57) constituting 52% of cases, the mean age was 77 years, range 65 - 93 years. Race: white (n = 79, 74.5%), African- American (n = 23, 21.2%), Asian (n = 4, 3.8%). Ethnicity: Latino (n = 8, 11.4%). Cases included hematologic cancers (n = 41, 37.6%), breast cancer (n = 19, 17.4%), prostate cancer (n = 15, 13.8%), gastrointestinal cancers (n = 10, 9.2%), and bladder and lung cancer each (n = 6, 5.5%). Low bone mass and osteoporosis was identified in 87 cases (80%). Only 26 cases reported falls in the preceding 6 months, while 11 cases had a prior fracture after the age of 50 years. Additional risk factors for falls and fractures included cognitive impairment, malnutrition, and polypharmacy. CONCLUSIONS Low bone mass and osteoporosis are highly prevalent conditions in older patients with hematologic and solid malignancies. A greater awareness of such, should allow for effective interventions in order to prevent fractures and their negative impact on quality of life.