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Tumor Marker Phenotype Concordance in Second Primary Breast Cancer. Monica Brown, MPH, PhD California Cancer Registry Mary Paré, RN, BS Sutter Cancer Center, Sacramento Katrina Bauer, MS, CTR California Cancer Registry. NAACCR 2009 Conference, June 13-19, San Diego. Introduction.
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Tumor Marker Phenotype Concordance in Second Primary Breast Cancer Monica Brown, MPH, PhD California Cancer Registry Mary Paré, RN, BS Sutter Cancer Center, Sacramento Katrina Bauer, MS, CTR California Cancer Registry NAACCR 2009 Conference, June 13-19, San Diego
Introduction • It’s estimated that 7% of women who have breast cancer will develop a subsequent second independent breast tumor within 10 years. • Risk factors for developing a second independent breast cancer are nearly same as for developing a first. • Patient survival is compromised by development of subsequent breast tumors.
Introduction, continued • Tumor receptors for estrogen (ER), progesterone (PR) and human growth hormone (HER2) are routinely assessed. • Patient’s clinical course & survival have been linked to tumor marker phenotype (TMP).
Introduction, continued • Patient’s clinical course and survival may also be impacted by TMP of subsequent primary tumors. • Our purpose was to… • determine TMP concordance between first (FPBC) and second primary breast cancers (SPBC) • describe demographic and clinical characteristics, and FPBC treatments associated with phenotype concordance.
Methods • 76,209 cases of female invasive breast cancer were identified in the California Cancer Registry from 1999-2004. • 1,407 women met study’s inclusion criteria • Had not undergone a prophylactic mastectomy as part of FPBC treatment. • Diagnosed with a SPBC during study period. • Status of all 3 tumor markers available.
Methods, continued • Pathologists of reporting facilities distinguished SPBCs & recurrences. • Considerations for distinguishing SPBCs were: • date of diagnosis • tumor histology • behavior • Laterality • CCR does not collect data on breast cancer recurrences.
Methods, continued • Laterality • Ipsilateral (same side), 169 (12%) • Contralateral, 1,238 (88%) • Time interval between diagnoses • Synchronous, <2 months, 894 (63.5%) • Metachronous, 2 months +, 513 (36.5%) • Tumor histology concordance • Concordant, 722 (51.3%) • Discordant, 685 (48.7%) SPBCs were grouped based on:
Results:Demographic Characteristics There were no significant change in age or SES between tumors
Tumor Characteristics SPBCs were significantly smaller, diagnosed at higher stage & were node positive
TMP Concordance PLA & TN SPBCs were more likely to be concordant, while HER2+ SPBCs were more likely to be discordant. Only TN SPBCs showed moderate, but significant concordance
Discordant Pairs, how were FPBC & SPBC Different? • 2% PLA & 53% HER2+ • ER- ER+ • 13.3% PLA & 45.3% HER2+ • PR- PR+ • 41% PLB & 33% HER2+ • HER2+ HER2- Better? Better? Better?
Model 1: Demographic & Clinical Predictors of TMP Concordance
Model 2: Demographic, Clinical & FPBC Treatment Predictors of TMP Concordance
Summary • Although SPBCs were determined to be independent, some results suggest otherwise. • Both TN breast cancer & chemotherapy have been associated with recurrence. • Discordant TMPs – loss/gain receptors • Changes in tumor marker receptors has been associated with chemotherapy & has been reported in metastases & recurrences .
Study Strengths & Limitations • Strengths • Population-based. • Race/ethnic and SES diversity of the breast cancer population in California. • Examined phenotypes not individual tumor markers. • Limitations • Phenotype status not validated. • Half of initial population lacked information on all 3 tumor marker – although found not to be statistically unique. • Did not have BRCA status – risk factor for SPBC.
Conclusion • The relationship between multiple primary breast cancer phenotype concordance and patient survival has yet to be determined. • Our study’s results indicate that SPBC surveillance strategies should include consideration of FPBC phenotype.
Conclusion • Although our study’s results are provocative, they may have been influenced by current criteria used to determine tumor independence. • This is troubling because, the trend is to use more sensitive imaging methods, such as MRI - more multiple tumors will be discovered. • But genomic methods, now used in research, which can tell us the relationship between multiple tumors – will soon be in use in the clinical setting.
Are cancer registries ready to … … record new genomic data? … document imaging methods? … address new criteria for distinguishing SPBCs from recurrences? Thank you!