Discordance in Hormone Receptor Status Among Primary, Metastatic, and Second Primary Breast Cancers: Biological Difference or Misclassification?

Background Bilateral breast cancer (BBC) may present as synchronous(SBC) or metachronous breast cancer(MBC). Optimal surgical management of BBC patients is not well defined. Here we report on histopathology, treatment, and outcomes in BBC patients. Methods Upon IRB approval, we identified BBC patients diagnosed and treated for invasive breast cancer between 1999–2007. Retrospective chart review for demographics, histopathology, treatment, and outcomes was performed. Factors associated with BCS choice were collected. Contraindication to BCS was defined as any of the following one-breast findings: multicentric disease; tumor considered too large for BCS; patient without a nominal breast size for acceptable cosmetic results. McNemar's test for matched pairs(binary variables) or the paired t-test(continuous variables) was used to examine if a pathologic characteristic differed within a cancer pair. Kaplan-Meier methods estimated overall survival(OS). Results 203 BBC patients(119 SBC,84 MBC) comprised our study group. Histopathologic characteristics of the first and second cancers diagnosed in both the SBC and MBC patients were very similar in histologic type and in molecular profiles. 57% of MBC patients underwent breast-conserving surgery at initial diagnosis versus 34% of patients with SBC. BCS contraindications were similar in both groups: 16(34%) of MBC and 28(36%) of SBC patients. Kaplan-Meier OS estimates at 5yrs/10yrs were 86%/78% for MBC, and 87%/77% for SBC patients, respectively. Conclusions OS was excellent for both MBC and SBC groups. Contraindications to breast-conserving surgery did not differ between groups. However, patients with SBC were less likely to undergo BCS compared to patients with MBC at time of initial diagnosis.

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“…18 It is a strength of our study that, being a single-institution study, the pathologic assessment was consistent for our patients.…”

Section: Discussionmentioning

confidence: 58%

Breast-Conserving Surgery in Bilateral Breast Cancer

O’Brien

Wright

et al. 2015

Ann Surg Oncol

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“…Let H i , i = 1,2 denote the true HR status (1 for positive and 0 for negative) and

H_{i}^{*}

denote the observed HR status for the i ‐th cancer. There are 1603 distinct values of

((), X_{1}, X_{2}, X_{3}, H_{1}^{*})

, which is a finer stratification than that used in where X 3 is dichotomized. It is worth noting that the method proposed in this paper differs from the method developed in in two aspects.…”

Section: Proposed Methodsmentioning

confidence: 99%

“…There are 1603 distinct values of

((), X_{1}, X_{2}, X_{3}, H_{1}^{*})

, which is a finer stratification than that used in where X 3 is dichotomized. It is worth noting that the method proposed in this paper differs from the method developed in in two aspects. First, the model for continuous X 3 is in a different parametric form to account for the curved relationship.…”

Section: Proposed Methodsmentioning

confidence: 99%

“…Hormone receptor positive and negative breast cancers have a fundamentally different natural history, leading to different prognosis and treatment strategies . For estrogen receptor positive cancers, tamoxifen and aromatase inhibitors are effective, but they have no effect in estrogen receptor negative cancers . A substantial amount of discordance in HR status (up to 40%) was reported between the two primary breast cancers of the same patient.…”

Section: Motivating Example: Discordance In Hormone Receptor Statusmentioning

confidence: 99%

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Bayesian adjustment for the misclassification in both dependent and independent variables with application to a breast cancer study

Liu

Gustafson

Huo

2016

Statistics in Medicine

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In this paper, we propose a Bayesian method to address misclassification errors in both independent and dependent variables. Our work is motivated by a study of women who have experienced new breast cancers on two separate occasions. We call both cancers primary, because the second is usually not considered as the result of a metastasis spreading from the first. Hormone receptors (HRs) are important in breast cancer biology, and it is well recognized that the measurement of HR status is subject to errors. This discordance in HR status for two primary breast cancers is of concern and might be an important reason for treatment failure. To sort out the information on true concordance rate from the observed concordance rate, we consider a logistic regression model for the association between the HR status of the two cancers and introduce the misclassification parameters (i.e., sensitivity and specificity) accounting for the misclassification in HR status. The prior distribution for sensitivity and specificity is based on how HR status is actually assessed in laboratory procedures. To account for the nonlinear effect of one error-free covariate, we introduce the B-spline terms in the logistic regression model. Our findings indicate that the true concordance rate of HR status between two primary cancers is greater than the observed value. Copyright © 2016 John Wiley & Sons, Ltd.

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“…Although loss of ER expression would appear to be a reasonable explanation for the emergence of endocrine resistance, studies of paired primary and metastatic tumor samples indicate that this occurs in only 10% of cases (Sighoko et al 2014). Similarly, Ellis et al (2008) found loss of ER expression during neoadjuvant endocrine therapy in less than 10% of patients, and notably in fewer than 20% of non-responders, who would be expected to represent an endocrine-resistant phenotype.…”

Section: Mechanisms Of Resistance: Esr1 Mutationsmentioning

confidence: 99%

Endocrine resistance in hormone-responsive breast cancer: mechanisms and therapeutic strategies

Murphy¹,

Dickler²

2016

Endocrine-Related Cancer

107

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The majority of breast cancers may be considered hormone responsive due to expression of hormone receptors (HR+). Although endocrine therapy is always considered for advanced HR+ breast cancer, the emergence of resistance is inevitable over time and is present from the start in a proportion of patients. In this review, we explore the mechanisms underlying de novo and acquired resistance to endocrine therapy. We comprehensively review newly approved and emerging therapies that have been developed to counteract specific mechanisms of resistance. We discuss the challenges pertinent to this therapeutic arena including the potential relief of negative regulatory feedback inhibition with compensatory pathway activation and the evolution of molecular changes in HR+ breast cancers during treatment. We discuss strategies to address these challenges in order to develop rational therapy approaches for patients with advanced HR+ breast cancer.

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Discordance in Hormone Receptor Status Among Primary, Metastatic, and Second Primary Breast Cancers: Biological Difference or Misclassification?

Cited by 44 publications

References 58 publications

Breast-Conserving Surgery in Bilateral Breast Cancer

Breast-Conserving Surgery in Bilateral Breast Cancer

Bayesian adjustment for the misclassification in both dependent and independent variables with application to a breast cancer study

Endocrine resistance in hormone-responsive breast cancer: mechanisms and therapeutic strategies

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