New biological therapies continue to emerge in breast cancer. Recent advances with anti-angiogenesis therapies and anti-HER2 therapies highlight the next generation of treatments that will be entering clinical practice. Important questions regarding these targeted treatments remain, however. There are uncertainties as to how best to integrate new drugs into existing treatment algorithms, whether to use monotherapy or combination therapy with chemotherapy, and how to manage novel side effects seen with these agents. This review highlights recent advances with the anti-vascular endothelial growth factor antibody, bevacizumab, and the dual-kinase inhibitor, lapatinib, in the treatment of metastatic breast cancer.
Erica L. Mayer, Nancy U. Lin, and Harold J. Burstein
Antonio Di Meglio, Nancy U. Lin, Rachel A. Freedman, William T. Barry, Eric P. Winer, and Ines Vaz-Luis
Background: When monitoring patients with metastatic breast cancer (mBC), the optimal strategies for imaging and utilization of tumor markers (TM) are uncertain. Patients and Methods: We used a retrospective cohort of 302 patients with de novo mBC treated from 2000 to 2012 at Dana-Farber Cancer Institute to describe the type and timing of imaging and TM testing during the first line of treatment (baseline, first, and subsequent testing). Results: At baseline, all patients had staging scans, with increasing use of PET/PET-CT (17.5% from 2000–2002; 40.3% from 2009–2012). PET/PET-CT was used by itself in only 12.5% of cases. Overall, 30.1% of patients, of whom 80.2% had no neurologic symptoms, underwent central nervous system (CNS) screening; 78.2% of patients had baseline TM testing. Over the course of treatment, 23.5% of patients had TM retested once a month or more. Time-to-first reimaging varied by disease site (hazard ratios for shorter time-to-first reimaging [95% CI] vs bone: brain, 4.27 [1.46–12.50]; liver, 2.19 [1.39–3.46]; lung, 2.75 [1.66–4.57]), but was not associated with tumor subtype or baseline TM testing, regardless of test results. First reimaging was prompted by an elevation in TM in only 1.4% of cases. There was weak correlation between frequency of imaging and TM tests (r=0.33; R2=0.11; P<.001). Discussion: Over time, we found an increased utilization of more sophisticated imaging staging techniques, such as PET/PET-CT scan, which was mostly requested in addition to other radiographic studies. CNS evaluations were frequently performed to screen asymptomatic patients. TM testing was often ordered, both at baseline and after treatment initiation. However, patterns of imaging utilization, although appropriately influenced by clinicopathologic factors such as disease site, did not appear to be impacted by TM testing. Conclusions: Studies focused on optimizing disease monitoring, including better integration of TM testing with imaging, are encouraged.
Katya Losk, Ines Vaz-Luis, Kristen Camuso, Rafael Batista, Max Lloyd, Mustafa Tukenmez, Mehra Golshan, Nancy U. Lin, and Craig A. Bunnell
Background: National guidelines endorse time-dependent quality metrics for breast cancer care. We examined factors associated with delays in chemotherapy initiation at an NCI-Designated Comprehensive Cancer Center. Patients and Methods: We identified 523 patients who received postoperative adjuvant chemotherapy between January 2011 and December 2013 at our center. We defined 28 days from last definitive surgery (LDS) to chemotherapy as the target time frame, and an unacceptable delay in chemotherapy initiation (UCD) as greater than 42 days from LDS. Multivariate regression models were used to identify factors associated with UCD and the impact of Oncotype DX testing in patients with hormone receptor (HR)–positive breast cancer. Results: Median days between LDS and chemotherapy initiation was 34 (interquartile range, 15), with 30% of patients starting within 28 days of LDS and 26.9% having UCD. Tumor characteristics such as subtype and stage affected UCD; patients with HR-positive or HER2-positive tumors were more likely to be delayed compared with those with triple-negative breast cancer. Patients with stage I disease, those undergoing mastectomy with or without immediate reconstruction, and those whose pathology sign-out was greater than 10 days postoperatively were more likely to be delayed. A higher proportion of UCD was found in HR-positive patients (31%) for whom Oncotype DX testing was ordered compared with those in whom it was not ordered (20%). Conclusions: This study provides insight into subpopulations that may be at risk to experience delays in chemotherapy initiation, directing interventions to improve the timeliness of care.
Sarah Asad, Carlos H. Barcenas, Richard J. Bleicher, Adam L. Cohen, Sara H. Javid, Ellis G. Levine, Nancy U. Lin, Beverly Moy, Joyce Niland, Antonio C. Wolff, Michael J. Hassett, and Daniel G. Stover
Background: Triple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. Our objective was to evaluate clinicopathologic and sociodemographic features associated with rrTNBC. Methods: We included patients diagnosed with stage I–III TNBC in 1996 through 2012 who received chemotherapy at 1 of 10 academic cancer centers. rrTNBC was defined as a distant metastatic recurrence event or death ≤24 months after diagnosis. Features associated with rrTNBC were included in a multivariable logistic model upon which backward elimination was performed with a P<.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts. Results: Among all patients with breast cancer treated at these centers, 3,016 fit the inclusion criteria. Training cohort (n=2,112) bivariable analyses identified disease stage, insurance type, age, body mass index, race, and income as being associated with rrTNBC (P<.10). In the final multivariable model, rrTNBC was significantly associated with higher disease stage (adjusted odds ratio for stage III vs I, 16.0; 95% CI, 9.8–26.2; P<.0001), Medicaid/indigent insurance, lower income (by 2000 US Census tract), and younger age at diagnosis. Model performance was consistent between the training and validation cohorts. In sensitivity analyses, insurance type, low income, and young age were associated with rrTNBC among patients with stage I/II but not stage III disease. When comparing rrTNBC versus late relapse (>24 months), we found that insurance type and young age remained significant. Conclusions: Timing of relapse in TNBC is associated with stage of disease and distinct sociodemographic features, including insurance type, income, and age at diagnosis.
Davinia S.E. Seah, Ines Vaz Luis, Erin Macrae, Jessica Sohl, Georgia Litsas, Eric P. Winer, Nancy U. Lin, and Harold J. Burstein
Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR+, TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR+ breast cancer, and 17 months for TNBC (P<.0001). Patients with HER2-amplified disease received the most lines (median, 4; P=.032) and the longest duration of chemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR+ and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.