Oncotype-DX recurrence score distribution in breast cancer patients with BRCA1/2 mutations

Lewin, Ruben F.; Sulkes, Aarón; Shochat, Tzippy; Tsoref, Daliah; Rizel, Shulamith; Liebermann, Nicky; Hendler, Daniel; Neiman, Victoria; Ben‐Aharon, Irit; Friedman, Eitan; Paluch‐Shimon, Shani; Margel, David; Kedar, Inbal; Yerushalmi, Rinat

doi:10.1007/s10549-016-3836-6

Cited by 31 publications

(36 citation statements)

References 26 publications

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“…To assess if positive lymph nodes tumors are associated with higher RS we combined the LN+ patients in our population and that of Lewin et al . series (again, excluding from the combined analysis our Clalit HMO LN+ patients to prevent overlap); of 14 LN+ patients low RS was found in 3 (21.4%), intermediate in 6 (42.8%) and high RS in 5 of them (35.7%), which is similar to the entire carrier population ( p = 0.81).…”

Section: Resultssupporting

confidence: 92%

“…The Oncotype Dx RS distribution of our carrier group and that of three previous studies compared with the general BC population are presented in Table . McAndrew et al .…”

Section: Resultsmentioning

confidence: 99%

“…McAndrew et al . reported similar RS distribution among carriers and noncarriers while our series and the other two BRCA populations exhibited significantly higher RS among carriers compared with controls. We combined our data with the RS distribution found in these three studies to enlarge BRCA population for comparison.…”

Section: Resultsmentioning

confidence: 99%

“…Among them 13 BRCA1 and 14 BRCA2 mutation carriers were identified. We combined our data with 3 recent studies of RS distribution in carriers and compared the entire cohort to data in the general BC population of 82,434 women published by Genomic Health . Patients from Israeli Clalit Health Services HMO described in our population data were excluded from the combined analysis to prevent overlap with the study population based on Clalit HMO database of Lewin et al …”

Section: Methodsmentioning

confidence: 99%

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Oncotype Dx recurrence score among BRCA1/2 germline mutation carriers with hormone receptors positive breast cancer

Halpern

Sonnenblick

Uziely

et al. 2017

Intl Journal of Cancer

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Gene expression assays are widely used to predict risk of recurrence in early breast cancer (BC). We report the 21-gene expression assay (Oncotype Dx) recurrence score (RS) distribution of 27 BRCA carriers with estrogen receptor (ER) positive BCs, identified at Hadassah Medical Center, combined with 2 previous studies. Treatment decision and outcomes of the 27 BRCA carriers were compared with an Israeli cohort of 1594 patients published recently. We found Oncotype Dx RS low (<18), intermediate (18-30) and high (>30) among 12 (21.4%), 23 (41.1%) and 21 (37.5%) of 56 BRCA1 carriers compared with 15 (17.2%), 49 (56.3%) and 23 (26.4%) of 87 BRCA2 carriers (p = 0.2). The corresponding distribution in a population of 82,434 women published by Genomic Health was 53.4%, 36.3% and 10.3% for low, intermediate and high RS (p < 0.001 for BRCA1 and BRCA2). Treatment decision regarding chemotherapy according to RS was similar in BRCA1, BRCA2 and the control group. Two of 27 carriers had distant recurrence: a BRCA1 carrier with RS of 18 and a BRCA2 carrier with RS of 22; both have an excellent response to chemotherapy. We found an approximately ∼3 fold increased rate of high RS among BRCA1 and 2 carriers with ER positive BC compared with the general BC population. These data might indicate that hormone positive BC in BRCA carriers are molecularly unique. The surprisingly good response to chemotherapy in the metastatic setting in 2 patients may suggest that the predictive value of low-intermediate RS in carriers merits further studies.

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Section: Resultssupporting

confidence: 92%

“…The Oncotype Dx RS distribution of our carrier group and that of three previous studies compared with the general BC population are presented in Table . McAndrew et al .…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Oncotype Dx recurrence score among BRCA1/2 germline mutation carriers with hormone receptors positive breast cancer

Halpern

Sonnenblick

Uziely

et al. 2017

Intl Journal of Cancer

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“…Mutation carriers were more likely than age-matched controls to have RS in the intermediate- or high-risk range and overall had higher median RS. This trend has been observed by other authors 58. Significantly, cases were also noted to have tumors of higher grade and lower PgR expression scores.…”

Section: Challenging Clinical Scenariossupporting

confidence: 86%

Clinical use of the Oncotype DX genomic test to guide treatment decisions for patients with invasive breast cancer

McVeigh¹,

Kerin²

2017

BCTT

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Implementation of the Oncotype DX assay has led to a change in the manner in which chemotherapy is utilized in patients with early stage, estrogen receptor (ER)-positive, node-negative breast cancer; ensuring that patients at highest risk of recurrence are prescribed systemic treatment, while at the same time sparing low-risk patients potential adverse events from therapy unlikely to influence their survival. This test generates a recurrence score between 0 and 100, which correlates with probability of distant disease recurrence. Patients with low-risk recurrence scores (0–17) are unlikely to derive significant survival benefit with adjuvant chemotherapy and hormonal agents derived from using adjuvant hormonal therapy only. Conversely, adjuvant chemotherapy has been shown to significantly improve survival in patients with high-risk recurrence scores (≥31). Trials are ongoing to determine how best to manage patients with recurrence scores in the intermediate range. This review outlines the introduction and impact of Oncotype DX testing on practice; ongoing clinical trials investigating its utility; and challenging clinical scenarios where the absolute recurrence score may require careful interpretation. We also performed a bibliometric analysis of publications on the topics of breast cancer and Oncotype DX as a surrogate marker of acceptability and incorporation of the assay into the management of patients with breast cancer.

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Patterns of recurrence and metastasis in BRCA1/BRCA2‐associated breast cancers

Song

Barry

Seah

et al. 2019

Cancer

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BACKGROUND: Breast cancer subtypes are associated with distinct metastatic patterns. Whether germline BRCA1/BRCA2 mutation status is independently associated with central nervous system (CNS) relapse, controlling for tumor subtype, is unknown. METHODS: Patients who were treated at Dana-Farber Cancer Institute and diagnosed with a first locoregional recurrence (LRR) or metastasis between 1981 and 2014 were identified using 2 institutional registries: 1) patients treated for recurrent breast cancer and 2) patients who underwent BRCA testing. The frequencies of LRR, sites of metastasis, and breast cancer-specific survival from LRR or metastasis were calculated, and the factors associated with CNS recurrence were evaluated using multivariable logistic regression models. RESULTS: The final study cohort included 30 BRCA1 mutation carriers, 32 BRCA2 mutation carriers, and 270 noncarriers. Most BRCA1 carriers (73%) had triple-negative breast cancer; whereas most BRCA2 carriers (72%) had hormone receptor-positive tumors. BRCA1 carriers frequently experienced lung and distant lymph node metastasis, whereas BRCA2 carriers and noncarriers most often experienced bone metastasis. Although CNS disease occurred frequently in both BRCA1 and BRCA2 carriers (53% BRCA1, 50% BRCA2, 25% noncarriers; P < .001), only BRCA2 mutation (P = .006) was significantly associated with CNS metastasis in multivariable analysis controlling for tumor subtype. BRCA2 mutation (P = .01), triple-negative subtype (P < .001), and the involvement of CNS (P < .001) and other non-CNS distant sites (relative to locoregional recurrence or contralateral disease; P < .001) at presentation of recurrent breast cancer were associated with risk for mortality. CONCLUSIONS: CNS involvement is frequent in women with germline BRCA1/BRCA2 mutations who have metastatic breast cancer. BRCA2 mutation carriers had a significantly higher frequency of CNS metastasis than noncarriers when controlling for breast cancer subtype.

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Oncotype-DX recurrence score distribution in breast cancer patients with BRCA1/2 mutations

Cited by 31 publications

References 26 publications

Oncotype Dx recurrence score among BRCA1/2 germline mutation carriers with hormone receptors positive breast cancer

Oncotype Dx recurrence score among BRCA1/2 germline mutation carriers with hormone receptors positive breast cancer

Clinical use of the Oncotype DX genomic test to guide treatment decisions for patients with invasive breast cancer

Patterns of recurrence and metastasis in BRCA1/BRCA2‐associated breast cancers

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