Faculty Bibliography

UNLABELLED:The PET Response Criteria in Solid Tumors (PERCIST) are not specific regarding the number of lesions that should be analyzed per patient. This study evaluated how the number of analyzed lesions affects response assessment in metastatic breast cancer. METHODS:In 60 patients, response was assessed by the change in SUVpeak, normalized to lean body mass, of the most (18)F-FDG-avid lesion (PERCIST 1) and by the change in the sum of normalized SUVpeak for up to 5 lesions (PERCIST 5). The correlation between response by PERCIST and progression-free and disease-specific survival was evaluated. RESULTS:In responders and nonresponders, the respective progression-free survival at 2 y was 37.26% and 6.43% for PERCIST 1 (P < 0.0001) and 33.65% and 7.14% for PERCIST 5 (P < 0.0001) and the respective disease-specific survival at 4 y was 58.96% and 25.44% for PERCIST 1 (P < 0.012) and 59.12% vs 20.01% for PERCIST 5 (P < 0.002). CONCLUSION:The number of analyzed lesions does not appear to have a major impact on the prognostic value of response assessment with (18)F-FDG PET/CT in metastatic breast cancer.

BACKGROUND:Inhibition of phosphatidylinositol 3-kinase (PI3K) is a promising approach to overcome resistance to endocrine therapy in breast cancer. Pictilisib is an oral inhibitor of multiple PI3K isoforms. The aim of this study is to establish if addition of pictilisib to fulvestrant can improve progression-free survival in oestrogen receptor-positive, endocrine-resistant breast cancer. METHODS:In this two-part, randomised, double-blind, placebo-controlled, phase 2 study, we recruited postmenopausal women aged 18 years or older with oestrogen receptor-positive, HER2-negative breast cancer resistant to treatment with an aromatase inhibitor in the adjuvant or metastatic setting, from 123 medical centres across 21 countries. Part 1 included patients with or without PIK3CA mutations, whereas part 2 included only patients with PIK3CA mutations. Patients were randomly allocated (1:1 in part 1 and 2:1 in part 2) via a computer-generated hierarchical randomisation algorithm to daily oral pictilisib (340 mg in part 1 and 260 mg in part 2) or placebo starting on day 15 of cycle 1, plus intramuscular fulvestrant 500 mg on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles in both groups. In part 1, we stratified patients by presence or absence of PIK3CA mutation, primary or secondary aromatase inhibitor resistance, and measurable or non-measurable disease. In part 2, we stratified patients by previous aromatase inhibitor treatment for advanced or metastatic disease or relapse during or within 6 months of an aromatase inhibitor treatment in the adjuvant setting and measurable or non-measurable disease. All patients and those administering treatment and assessing outcomes were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population for both parts 1 and 2 and also separately in patients with PIK3CA-mutated tumours in part 1. Tumour assessment (physical examination and imaging scans) was investigator-assessed and done at screening and after 8 weeks, 16 weeks, 24 weeks, and 32 weeks of treatment from day 1 of cycle 1 and every 12 weeks thereafter. We assessed safety in as-treated patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT01437566. FINDINGS/RESULTS:In part 1, between Sept 27, 2011, and Jan 11, 2013, we randomly allocated 168 patients to the pictilisib (89 [53%]) or placebo (79 [47%]) group. In part 2, between March 18, 2013, and Jan 2, 2014, we randomly allocated 61 patients to the pictilisib (41 [67%]) or placebo (20 [33%]) group. In part 1, we found no difference in median progression-free survival between the pictilisib (6·6 months [95% CI 3·9-9·8]) and placebo (5·1 months [3·6-7·3]) group (hazard ratio [HR] 0·74 [95% CI 0·52-1·06]; p=0·096). We also found no difference when patients were analysed according to presence (pictilisib 6·5 months [95% CI 3·7-9·8] vs placebo 5·1 months [2·6-10·4]; HR 0·73 [95% CI 0·42-1·28]; p=0·268) or absence (5·8 months [3·6-11·1] vs 3·6 months [2·8-7·3]; HR 0·72 [0·42-1·23]; p=0·23) of PIK3CA mutation. In part 2, we also found no difference in progression-free survival between groups (5·4 months [95% CI 3·8-8·3] vs 10·0 months [3·6-13·0]; HR 1·07 [95% CI 0·53-2·18]; p=0·84). In part 1, grade 3 or worse adverse events occurred in 54 (61%) of 89 patients in the pictilisib group and 22 (28%) of 79 in the placebo group. 19 serious adverse events related to pictilisib treatment were reported in 14 (16%) of 89 patients. Only one (1%) of 79 patients reported treatment-related serious adverse events in the placebo group. In part 2, grade 3 or worse adverse events occurred in 15 (36%) of 42 patients in the pictilisib group and seven (37%) of 19 patients in the placebo group. Four serious adverse events related to pictilisib treatment were reported in two (5%) of 42 patients. One treatment-related serious adverse event occurred in one (5%) of 19 patients in the placebo group. INTERPRETATION/CONCLUSIONS:Although addition of pictilisib to fulvestrant did not significantly improve progression-free survival, dosing of pictilisib was limited by toxicity, potentially limiting its efficacy. For future assessment of PI3K inhibition as an approach to overcome resistance to hormonal therapy, inhibitors with greater selectivity than that of pictilisib might be needed to improve tolerability and potentially increase efficacy. No further investigation of pictilisib in this setting is ongoing. FUNDING/BACKGROUND:F Hoffmann-La Roche.

PURPOSE:A cancer and fertility program was established at a large cancer center to support clinicians in discussing treatment-related fertility risks and fertility preservation (FP) options with patients and in referring patients to reproductive specialists. The program provides resources, clinician education, and fertility clinical nurse specialist consultation. This study evaluated the program's impact on patient satisfaction with information received. PATIENTS AND METHODS:Retrospective cross-sectional surveys assessed satisfaction before (cohort 1 [C1]) and after (cohort 2 [C2]) program initiation. Questionnaires were investigator-designed, gender-specific, and anonymous. RESULTS:Most C1 (150 males, 271 females) and C2 (120 males, 320 females) respondents were 2 years postdiagnosis; the most frequently reported cancers were testicular, breast, and lymphoma. A significant difference in satisfaction with the amount of information received was seen between C1 and C2. For males, satisfaction with information on fertility risks was high in both cohorts but significantly greater in C2 for information on sperm banking (χ(2) = 9.3, P = .01) and finding a sperm bank (χ(2) = 13.3, P = .001). For females, satisfaction with information was significantly greater in C2 for information on fertility risks (χ(2) = 62.1, P < .001), FP options (χ(2) = 71.9, P < .001), help with decision making (χ(2) = 80.2, P < .001), and finding a reproductive endocrinologist (χ(2) = 60.5, P < .001). Among patients who received and read information materials, 96% of males and 99% of females found them helpful. Among C2 females, fertility clinical nurse specialist consultation was associated with significantly greater satisfaction with information on FP options (χ(2) = 11.2, P = .004), help with decision making (χ(2) = 10.4, P = .006), and finding a reproductive endocrinologist (χ(2) = 22.6, P < .001), with 10% reporting lack of knowledge as a reason for not pursuing FP. CONCLUSION:Improvements in patient satisfaction with information received demonstrate the potential for fertility programs in cancer care settings to improve the quality of clinician-patient discussions about fertility.

BACKGROUND:Biological differences between BRCA-associated breast cancer and sporadic breast cancer may warrant different adjuvant chemotherapy (ACRx) recommendations despite similar phenotypic features. A 21-gene expression profile (Oncotype DX) generates a prognostic recurrence score (RS) that predicts the ACRx benefit in patients with hormone receptor-positive breast cancer. No reports describe assay results for BRCA-associated breast cancer. METHODS:A review of Memorial Sloan Kettering Cancer Center databases identified 4908 patients with hormone receptor-positive, node-negative breast cancer who underwent Oncotype DX testing between July 2006 and March 2014. BRCA1/BRCA2 carriers (cases) were identified and matched (1:2) by age at diagnosis and tumor size to noncarrier controls. Two-sample nonparametric tests were used to compare the baseline characteristics, RSs, and risk stratification between BRCA1 and BRCA2 patients. Conditional logistic regression was used to assess these differences by mutational status. RESULTS:Fifty mutation-associated cases (19 BRCA1 cases and 31 BRCA2 cases) and 100 controls who were well matched for age (P = .9) and tumor size (P = .6) were included. BRCA1 and BRCA2 carriers had similar median RSs (P = .6) and risk category stratification (P = .3). The median RS was higher for cases versus controls (24 vs 16; P < .0001). Risk stratification also differed by mutational status (P = .0002). Cases had more high-risk disease (28% vs 7%) and intermediate-risk disease (56% vs 36%) and less low-risk disease (16% vs 57%). Cases were more likely than controls to receive ACRx (74% vs 46%; P = .002). CONCLUSIONS:Germline BRCA-associated hormone receptor-positive breast cancer may be associated with intrinsically less favorable biology. Few affected carriers have RS indicating a clear absence of benefit from ACRx. The increased use of ACRx and benefit from ACRx in BRCA carriers may mitigate otherwise inferior outcomes.

The success of breast cancer therapy is ultimately defined by clinical endpoints such as survival. It is valuable to have biomarkers that can predict the most efficacious therapies or measure response to therapy early in the course of treatment. Molecular imaging has a promising role in complementing and overcoming some of the limitations of traditional biomarkers by providing the ability to perform noninvasive, repeatable whole-body assessments. The potential advantages of imaging biomarkers are obvious and initial clinical studies have been promising, but proof of clinical utility still requires prospective multicenter clinical trials.

OBJECTIVE:Many patients with cancer search out information about their cancer on the internet, thus affecting their relationship with their oncologists. An in-depth analysis of patient-physician communication about information obtained from the internet is currently lacking. METHODS:We audio-recorded visits of patients with breast cancer and their oncologists where internet information was expected to be discussed. Inductive thematic text analysis was used to identify qualitative themes from these conversations. RESULTS:Twenty-one patients self-reported discussing cancer-related internet information (CRII) with their oncologists; 16 audio recordings contained detectable discussions of CRII and were analyzed. Results indicated that oncologists and patients initiated CRII discussions implicitly and explicitly. Oncologists responded positively to patient-initiated CRII discussions by (1) acknowledging their limited expertise/knowledge, (2) encouraging/approving using the internet as an information resource, (3) providing information/guidance on the proper use of internet searches, (4) discussing the pros and cons of relevant treatment options, or (5) giving information. Finally, patients reacted to the CRII discussions by (1) indicating that they only used reputable sources/websites, (2) asking for further explanation of information, (3) expressing continued concern, or (4) asking for the oncologist's opinion or recommendation. CONCLUSIONS:These results indicate that the majority of patients introduce internet information implicitly, in order to guard against any threat to their self-esteem. Physicians, in turn, seem to respond in a supportive fashion to reduce any threat experienced. Future interventions may consider providing prescription-based guidance on how to navigate the internet as a health information resource and to encourage patients to bring these topics up with their oncologist.

Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor (ER)-positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions.