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Baseline staging imaging for distant metastasis in women with stages I, II, and III breast cancer.

ABSTRACT: Background:In Ontario, there is no clearly defined standard of care for staging for distant metastasis in women with newly diagnosed and biopsy-confirmed breast cancer whose clinical presentation is suggestive of early-stage disease. This guideline addresses baseline imaging investigations for women with newly diagnosed primary breast cancer who are otherwise asymptomatic for distant metastasis. Methods:The medline and embase databases were systematically searched for evidence from January 2000 to April 2019, and the best available evidence was used to draft recommendations relevant to the use of baseline imaging investigation in women with newly diagnosed primary breast cancer who are otherwise asymptomatic. Final approval of this practice guideline was obtained from both the Staging in Early Stage Breast Cancer Advisory Committee and the Report Approval Panel of the Program in Evidence-Based Care. Recommendations:These recommendations apply to all women with newly diagnosed primary breast cancer (originating in the breast) who have no symptoms of distant metastasis Staging tests using conventional anatomic imaging [chest radiography, liver ultrasonography, chest-abdomen-pelvis computed tomography (ct)] or metabolic imaging modalities [integrated positron-emission tomography (pet)/ct, integrated pet/magnetic resonance imaging (mri), bone scintigraphy] should not be routinely ordered for women newly diagnosed with clinical stage i or stage ii breast cancer who have no symptoms of distant metastasis, regardless of biomarker status. In women newly diagnosed with stage iii breast cancer, baseline staging tests using either anatomic imaging (chest radiography, liver ultrasonography, chest-abdomen-pelvis ct) or metabolic imaging modalities (pet/ct, pet/mri, bone scintigraphy) should be considered regardless of whether the patient is symptomatic for distant metastasis and regardless of biomarker profile.

SUBMITTER: Arnaout A

PROVIDER: S-EPMC7253735 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Baseline staging imaging for distant metastasis in women with stages I, II, and III breast cancer.

Arnaout A A Varela N P NP Allarakhia M M Grimard L L Hey A A Lau J J Thain L L Eisen A A

Current oncology (Toronto, Ont.) 20200401 2

<h4>Background</h4>In Ontario, there is no clearly defined standard of care for staging for distant metastasis in women with newly diagnosed and biopsy-confirmed breast cancer whose clinical presentation is suggestive of early-stage disease. This guideline addresses baseline imaging investigations for women with newly diagnosed primary breast cancer who are otherwise asymptomatic for distant metastasis.<h4>Methods</h4>The medline and embase databases were systematically searched for evidence fro ...[more]

PMID: 32489262

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Project description:BackgroundDespite 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 methodsA 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.ResultsAmong 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.ConclusionIn 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 practiceDespite 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.

Project description:BackgroundDevelopment of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive.MethodsWe have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database.ResultsIn this study, we identified an association between NOTCH3 expression and development of metastases in ERα+ and TNBC models. ERα+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERαhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens.ConclusionsThese findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer.

Project description:ObjectivesTo estimate the long term risk of distant metastases (DM) for women with initial diagnoses of non-metastatic breast cancer; to estimate breast cancer-specific and overall survival for women with DM.DesignPopulation-based health record linkage study.Setting, participantsWomen diagnosed with localised or regional primary breast cancer recorded in the NSW Cancer Registry, 2001-2002.Major outcome measuresTime from breast cancer diagnosis to first DM, time from first DM to death from breast cancer.Secondary outcometime to death from any cause.Results6338 women were diagnosed with non-metastatic breast cancer (localised, 3885; regional, 2453; median age, 59 years [IQR, 49-69 years]). DM were recorded (to 30 September 2016) for 1432 women (23%; median age, 62 years [IQR, 51-73 years]). The 14-year cumulative DM incidence was 22.2% (95% CI, 21.1-23.2%; localised disease: 14.3% [95% CI, 13.2-15.4%]; regional disease: 34.7% [95% CI, 32.8-36.6%]). Annual hazard of DM was highest during the second year after breast cancer diagnosis (localised disease: 2.8%; 95% CI, 2.3-3.3%; regional disease: 9.1%; 95% CI, 7.8-10.3%); from year five it was about 1% for those with localised disease, from year seven about 2% for women with regional disease at diagnosis. Five years after diagnosis, the 5-year conditional probability of DM was 4.4% (95% CI, 3.7-5.1%) for women with localised and 10.4% (95% CI, 9.1-12.0%) for those with regional disease at diagnosis. Median breast cancer-specific survival from first DM record date was 28 months (95% CI, 25-31 months); the annual hazard of breast cancer death after the first DM record declined from 36% (95% CI, 33-40%) during the first year to 14% (95% CI, 11-18%) during the fourth year since detection.ConclusionsDM risk declines with time from diagnosis of non-metastatic breast cancer, and the annual risk of dying from breast cancer declines with time from initial DM detection. These findings can be used to inform patients at follow-up about changes in risk over time since diagnosis and for planning health services.

Dataset Information

Baseline staging imaging for distant metastasis in women with stages I, II, and III breast cancer.

Publications

Baseline staging imaging for distant metastasis in women with stages I, II, and III breast cancer.

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