Publications by authors named "Brittany L Bychkovsky"

11 Publications

  • Page 1 of 1

Identifying Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.

JCO Precis Oncol 2019 15;3. Epub 2019 Nov 15.

Dana-Farber Cancer Institute, Boston, MA.

Purpose: The yield of comprehensive genomic profiling in recruiting patients to molecular-based trials designed for small subgroups has not been fully evaluated. We evaluated the likelihood of enrollment in a clinical trial that required the identification of a specific genomic change based on our institute-wide genomic tumor profiling.

Patients And Methods: Using genomic profiling from archived tissue samples derived from patients with metastatic breast cancer treated between 2011 and 2017, we assessed the impact of systematic genomic characterization on enrollment in an ongoing phase II trial (ClinicalTrials.gov identifier: NCT01670877). Our primary aim was to describe the proportion of patients with a qualifying mutation identified by our institutional genomic panel (OncoMap or OncoPanel) who enrolled in the trial. Secondary objectives included median time from testing result to trial registration, description of the spectrum of mutations, and survival. Associations were calculated using Fisher's exact test.

Results: We identified a total of 1,045 patients with metastatic breast cancer without amplification who had available genomic testing results. Of these, 42 patients were found to have mutation and 19 patients (1.8%) were eligible for the trial on the basis of the presence of an activating mutation, 18 of which were identified by OncoPanel testing. Fifty-eight percent of potentially eligible patients were approached, and 33.3% of eligible patients enrolled in the trial guided exclusively by OncoPanel testing.

Conclusion: More than one half of eligible patients were approached for trial participation and, significantly, one third of those were enrolled in NCT01670877. Our data illustrate the ability to enroll patients in trials of rare subsets in routine clinical practice and highlight the need for these broadly based approaches to effectively support the success of these studies.
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http://dx.doi.org/10.1200/PO.19.00087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446367PMC
November 2019

Are rare cancer survivors at elevated risk of subsequent new cancers?

BMC Cancer 2019 Feb 21;19(1):166. Epub 2019 Feb 21.

Department of Medicine, Dana-Farber Cancer Institute & Harvard Medical School, Boston, MA, USA.

Background: Although rare cancers account for 27% of cancer diagnoses in the US, there is insufficient research on survivorship issues in these patients. An important issue cancer survivors face is an elevated risk of being diagnosed with new primary cancers. The primary aim of this analysis was to assess whether a history of rare cancer increases the risk of subsequent cancer compared to survivors of common cancers.

Methods: This was a prospective cohort study of 16,630 adults with personal and/or family history of cancer who were recruited from cancer clinics at 14 geographically dispersed US academic centers of the NIH-sponsored Cancer Genetics Network (CGN). Participants' self-reported cancer histories were collected at registration to the CGN and updated annually during follow-up. At enrollment, 14% of participants reported a prior rare cancer. Elevated risk was assessed via the cause-specific hazard ratio on the time to a subsequent cancer diagnosis.

Results: After a median follow-up of 7.9 years, relative to the participants who were unaffected at enrollment, those with a prior rare cancer had a 23% higher risk of subsequent cancer (95% CI: -1 to 52%), while those with a prior common cancer had no excess risk. Patients having two or more prior cancers were at a 53% elevated risk over those with fewer than two (95% CI: 21 to 94%) and if the multiple prior cancers were rare cancers, risk was further elevated by 47% (95% CI: 1 to 114%).

Conclusion: There is evidence suggesting that survivors of rare cancers, especially those with multiple cancer diagnoses, are at an increased risk of a subsequent cancer. There is a need to study this population more closely to better understand cancer pathogenesis.
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http://dx.doi.org/10.1186/s12885-019-5358-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385466PMC
February 2019

Cancer Pathology Turnaround Time at Queen Elizabeth Central Hospital, the Largest Referral Center in Malawi for Oncology Patients.

J Glob Oncol 2017 Dec 11;3(6):734-739. Epub 2017 Apr 11.

Leo P.L. Masamba and Petani E. Mtonga, Queen Elizabeth Central Hospital; Linda Kalilani Phiri, University of Malawi College of Medicine, Blantyre, Malawi; Brittany L. Bychkovsky, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.

Purpose In all settings, a need exists for expedited pathology processing for patients with a suspected cancer diagnosis. In low- and middle-income countries (LMICs) with limited resources, processing pathology samples is particularly challenging, so the measurement of turnaround times (TATs) for pathology results is an important quality metric. We explored the pathology TAT for suspected cancer patients at Queen Elizabeth Central Hospital in Malawi to determine whether a difference exists when patients paid an out-of-pocket fee (paid for [PF] v nonpaid for [NPF]) to facilitate sample processing. Methods and Population This retrospective descriptive study included all patients with suspected cancer (N = 544) who underwent incisional and excisional biopsy in 2010 at Queen Elizabeth Central Hospital, a teaching hospital in Malawi. Data were abstracted from patient charts and administrative forms to build a database and determine the TAT for PF and NPF samples. Results The median TAT for the 544 patients was 71 days (interquartile range [IQR], 31 to 118 days). The median pathology processing time was 31 days (IQR, 15 to 52 days) and was shorter for PF versus NPF samples. The median TAT was 43 days for PF samples (IQR, 27 to 69 days) versus 101 days for NPF samples (IQR, 31 to 118 days), which was significantly different by the Wilcoxon rank sum test ( P < .01). Conclusion The TAT for pathology samples among patients with suspected cancer was longer than reported for other African countries during the study period, was longer than considered acceptable in high-income countries, and differed between PF and NPF samples.
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http://dx.doi.org/10.1200/JGO.2015.000257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735957PMC
December 2017

Compulsory Licenses for Cancer Drugs: Does Circumventing Patent Rights Improve Access to Oncology Medications?

J Glob Oncol 2016 Oct 29;2(5):292-301. Epub 2016 Jun 29.

, Centro Paulista de Oncologia, and Oncoclinicas do Brasil; , Oncoclinicas Group, Sao Paulo, Brazil; , Dana-Farber Cancer Center Harvard Medical School, Boston, MA; and , Johns Hopkins University School of Medicine, Baltimore, MD.

Worldwide, there are enormous inequities in cancer control that cause poor outcomes among patients with cancer who live in low- and middle-income countries (LMICs). One of the biggest challenges that oncology faces today is how to increase patient access to expensive, but life-saving, therapies in LMICs. Access to cancer medications in LMICs is a major problem, especially in recent years, as the costs of these therapies continue to rise exponentially. One mechanism available to LMICs to improve access to cancer medications allows a country to pursue a compulsory license for a given drug. Here, we will review how the legal framework in the World Trade Organization's Trade-Related Aspects of Intellectual Property Rights Agreement and the Doha Declaration supports countries to circumvent patent laws and acquire compulsory licenses for essential medicines. We will also discuss the current and future role of compulsory licenses in oncology and how compulsory licenses may improve access to cancer drugs in LMICs.
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http://dx.doi.org/10.1200/JGO.2016.005363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493268PMC
October 2016

Systemic Therapies for Nonmetastatic Breast Cancer: The Role of Neoadjuvant and Adjuvant Chemotherapy and the Use of Endocrine Therapy.

Clin Obstet Gynecol 2016 12;59(4):756-771

*Dana-Farber Cancer Institute †Harvard Medical School ‡Massachusetts General Hospital Cancer Center, Boston, Massachusetts §Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Alpert Medical School of Brown University, Providence, Rhode Island.

Breast cancer is a heterogenous disease, comprised of at least 3 major subtypes: hormone receptor-positive/HER2-(HR+), HER2+, and HR-/HER2-(triple negative) breast cancers. The medical management of each subype is distinct. In this article, we review contemporary data supporting the use of chemotherapy, endocrine therapy and biologic therapies, especially HER2-directed agents, in the adjuvant and neoadjuvant setting in patients with newly diagnosed nonmetastatic (stage I-III) breast cancer.
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http://dx.doi.org/10.1097/GRF.0000000000000237DOI Listing
December 2016

Use and Yield of Baseline Imaging and Laboratory Testing in Stage II Breast Cancer.

Oncologist 2016 12 22;21(12):1495-1501. Epub 2016 Aug 22.

Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Background: Despite guideline recommendations, baseline laboratory testing and advanced imaging are widely ordered in clinical practice to stage asymptomatic patients with clinical stage II breast cancer (BC).

Materials And Methods: A retrospective study at two academic centers in Boston, Massachusetts, between 2006 and 2007 explored the use, results, and implications of laboratory tests, tumor markers, and imaging in patients with clinical stage II BC.

Results: Among 411 patients, 233 (57%) had liver function testing, 134 (33%) had tumor marker tests, and 237 (58%) had computed tomography (CT) as part of their initial diagnostic workup. Median age was 52 (range, 23-90 years). On multivariable analysis, young age, more advanced stage, and tumor subtype (human epidermal growth receptor-positive [HER2+] and triple-negative breast cancer [TNBC]) were significantly associated with baseline CT. The rate of detection of true metastatic disease with use of baseline staging imaging was 2.1% (95% confidence interval, 0.7%-5%). It was 2.2% (3 of 135) for estrogen receptor/progesterone receptor-positive disease, 1.9% (1 of 54) for HER2+ disease, and 2.1% (1 of 48) for TNBC. At 5 years of follow-up, 46 of 406 patients were diagnosed with metastatic breast cancer. Thirty-four of 46 (73.9%) who developed recurrent disease had imaging at their initial diagnosis, and of these, five had abnormalities on their initial imaging that was correlated with where they developed metastatic disease.

Conclusion: In this cohort of women with stage II BC, staging imaging at diagnosis had a low yield in detecting distant metastases (2.1%). The detection rate was not higher with HER2+ disease or TNBC, despite the trend that patients with these subtypes were more likely to undergo imaging.

Implications For Practice: Despite guideline recommendations, asymptomatic patients with stage II breast cancer (BC) often undergo staging imaging with computed tomography, bone scanning, or positron emission tomography. Physicians have often reported that they order imaging despite recommendations because they believe that younger patients or patients with more aggressive BC phenotypes, such as human epidermal receptor 2-positive BC or triple-negative BC, benefit from staging imaging. In this cohort of women younger than those in prior studies, the yield of detecting distant metastatic disease in patients with clinical stage II BC was very low and the detection rate was not higher in the presence of HER2-positive or triple-negative BC.
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http://dx.doi.org/10.1634/theoncologist.2016-0157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153340PMC
December 2016

Imaging in the evaluation and follow-up of early and advanced breast cancer: When, why, and how often?

Breast 2017 Feb 13;31:318-324. Epub 2016 Jul 13.

Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:

Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0-II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0-III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging.
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http://dx.doi.org/10.1016/j.breast.2016.06.017DOI Listing
February 2017

Poor persistence with hormonal therapy among women with breast cancer.

J Geriatr Oncol 2016 05 28;7(3):154-7. Epub 2016 Apr 28.

Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA(Editorial accompanies Jacob et al. "Age-related differences in persistence in women with breast cancer treated with tamoxifen or aromatase inhibitors in Germany"). Electronic address:

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http://dx.doi.org/10.1016/j.jgo.2016.04.002DOI Listing
May 2016

Cervical cancer control in Latin America: A call to action.

Cancer 2016 Feb 15;122(4):502-14. Epub 2015 Dec 15.

Harvard Medical School, Boston, Massachusetts.

Cervical cancer (CC) is second most common cause of cancer in Latin America and is a leading cause of cancer mortality among women. In 2015, an estimated 74,488 women will be diagnosed with CC in Latin America and 31,303 will die of the disease. CC mortality is projected to increase by 45% by 2030 despite human papillomavirus (HPV) vaccination and screening efforts. In this setting, the goal was of the current study was to examine CC control efforts in Latin America and identify deficiencies in these efforts that could be addressed to reduce CC incidence and mortality. The authors found that HPV vaccination has been introduced in the majority of Latin American countries, and there is now a need to monitor the success (or shortcomings) of these programs and to ensure that these programs are sustainable. This topic was also reviewed in light of emerging data demonstrating that visual inspection with acetic acid and HPV DNA testing without Papanicolaou tests have efficacy from a screening perspective and are good alternatives to cytology-based screening programs. Overall, there is a need to build capacity for CC control in Latin America and the best strategy will depend on the country/region and must be tailored to meet the needs of the population as well as available resources.
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http://dx.doi.org/10.1002/cncr.29813DOI Listing
February 2016

Progress and remaining challenges for cancer control in Latin America and the Caribbean.

Lancet Oncol 2015 Oct;16(14):1405-38

The Global Cancer Institute, Boston, MA, USA; Avon International Breast Cancer Research Program, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.
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http://dx.doi.org/10.1016/S1470-2045(15)00218-1DOI Listing
October 2015

Older women's experience with breast cancer treatment decisions.

Breast Cancer Res Treat 2014 May 31;145(1):211-23. Epub 2014 Mar 31.

Division of General Medicine and Primary Care, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, 1309 Beacon, Office 219, Brookline, Boston, MA, 02446, USA,

The purpose of this study was to better understand older women's experience with breast cancer treatment decisions. We conducted a longitudinal study of non-demented, English-speaking women ≥ 65 years recruited from three Boston-based breast imaging centers. We interviewed women at the time of breast biopsy (before they knew their results) and 6 months later. At baseline, we assessed intention to accept different breast cancer treatments, sociodemographic, and health characteristics. At follow-up, we asked women about their involvement in treatment decisions, to describe how they chose a treatment, and influencing factors. We assessed tumor characteristics through chart abstraction. We used quantitative and qualitative analyses. Seventy women (43 ≥ 75 years) completed both interviews and were diagnosed with breast cancer; 91 % were non-Hispanic white. At baseline, women 75+ were less likely than women 65-74 to report that they would accept surgery and/or take a medication for ≥ 5 years if recommended for breast disease. Women 75+ were ultimately less likely to receive hormonal therapy for estrogen receptor positive tumors than women 65-74. Women 75+ asked their surgeons fewer questions about their treatment options and were less likely to seek information from other sources. A surgeon's recommendation was the most influential factor affecting older women's treatment decisions. In open-ended comments, 17 women reported having no perceived choice about treatment and 42 stated they simply followed their physician's recommendation for at least one treatment choice. In conclusion, to improve care of older women with breast cancer, interventions are needed to increase their engagement in treatment decision-making.
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http://dx.doi.org/10.1007/s10549-014-2921-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117244PMC
May 2014