Breast cancer biomarkers before and after neoadjuvant chemotherapy: does repeat testing impact therapeutic management?

Xian, Zhaoying; Quinones, Alexander; Tozbikian, Gary; Zynger, Debra L.

doi:10.1016/j.humpath.2016.12.019

Cited by 28 publications

(24 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, alterations of ER, PR, and HER2 status were observed in 4.1%, 18.1%, and 3.4% of the total cases, respectively. PR status changed more often than that of ER and HER2, which is consistent with previous reports [ 12 , 21 - 23 ]. The frequency of positive to negative conversion was higher than negative to positive.…”

Section: Discussionsupporting

confidence: 93%

“…Zhou et al [ 22 ] also showed that the luminal B and luminal–HER2 subtypes underwent biomarker alterations after PST more frequently than the other subtypes, although the differences were not statistically significant except for the Ki-67 index [ 22 ]. Recently, Xian et al [ 23 ] reported that the triplenegative subtype usually remained triple-negative after PST, and PR was the most frequently altered biomarker. Currently, there are no guidelines about whether treatment should be modified based on altered biomarker status after PST.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer

Ahn

Kim

et al. 2018

Cancer Res Treat

View full text Add to dashboard Cite

PurposeAlteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST.Materials and MethodsThe pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed.ResultsEstrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup.ConclusionER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer

Ahn

Kim

et al. 2018

Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…Reports of resection specimens without a primary tumor were excluded. Likewise, pathology reports of patients who received neoadjuvant treatment were excluded as tumor receptor status may be converted by neo-adjuvant treatment [ 40 – 42 ] (Fig. 1 ).…”

Section: Methodsmentioning

confidence: 99%

Hormone- and HER2-receptor assessment in 33,046 breast cancer patients: a nationwide comparison of positivity rates between pathology laboratories in the Netherlands

Dooijeweert

Deckers²,

Baas

et al. 2019

Breast Cancer Res Treat

View full text Add to dashboard Cite

Purpose Patient management of invasive breast cancer (IBC) is to a large extent based on hormone- and HER2-receptor assessment. High-quality, reliable receptor assessment is of key importance as false results may lead to under- or overtreatment of patients. Surveillance of case-mix adjusted positivity rates has been suggested as a tool to identify laboratories with insufficient testing assays, as this covers the whole process of receptor assessment and enables laboratories to benchmark their positivity rates against other laboratories. We studied laboratory-specific variation in hormone- and HER2 positivity rates of 33,046 breast cancer patients using real-life nationwide data. Methods All synoptic pathology reports of IBC resection-specimens, obtained between 2013 and 2016, were retrieved from the nationwide Dutch pathology registry (PALGA). Absolute and case-mix adjusted receptor positivity rates were compared to the mean national proportion and presented in funnel plots in separate analyses for estrogen (ER), progesterone (PR) and HER2. Case-mix adjustment was performed by multivariable logistic regression. Results 33,794 IBC lesions from 33,046 patients of 39 pathology laboratories were included. After case-mix adjustment, mean positivity rates were 87.2% for ER (range 80.4–94.3), 71.3% for PR (62.5–77.5%), and 9.9% for HER2 (5.5–12.7%). Overall, 14 (35.9%), 17 (43.6%) and 11 (28.2%) laboratories showed positivity rates outside the 95% confidence interval for ER, PR and HER2, respectively. Conclusion This nationwide study shows that absolute variation in hormone- and HER2-receptor positivity rates between Dutch pathology laboratories is limited. Yet, the considerable number of outlying laboratories shows that there is still need for improvement. Continuous monitoring and benchmarking of positivity rates may help to realize this.

show abstract

“…Hormone receptor status changed more often than HER2 status, and as for hormone receptors, positive to negative conversion was more common than negative to positive conversion [51,52]. The frequency of HER2 change after NAC is reported in up to 15%, and both positive to negative conversion and negative to positive conversion were found with no preponderance [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66]. Previous studies on HER2 change after NAC are summarized in Table 4.…”

Section: Changes In Her2 Status After Neoadjuvant Chemotherapymentioning

confidence: 99%

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

Ahn

Woo

Lee

et al. 2020

J Pathol Transl Med

169

View full text Add to dashboard Cite

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Human epidermal growth factor receptor 2 (HER2) is a protooncogene that encodes epidermal growth factor receptor with tyrosine kinase activity, located on chromosome 17 at q21. In breast cancers, HER2 gene is amplified in 15%-20% of invasive breast cancers and its amplification is closely linked to HER2 protein overexpression [1,2]. HER2 amplification is a poor prognostic factor associated with a high rate of recurrence and mortality, and is a predictive factor for response to anthracyclinebased chemotherapies in patients with breast cancer [1,2]. Most importantly, it is a sole predictive marker for treatment benefits from HER2-targeting agents such as trastuzumab, lapatinib, and pertuzumab. As HER2-targeted therapy is exclusively effective in HER2-overexpressed and/or HER2-amplified breast cancers, precise assessment of HER2 status is an essential step for treatment of breast cancer. In this review, we focused on changes in the American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines on HER2 interpretation and some pitfalls in the interpretation of HER2 status in breast cancers. METHODS OF HER2 TESTINGCurrently, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and chromogenic in situ hybridization (CISH) including silver in situ hybridization (SISH) are regarded as standard methods for determination of HER2 status in breast cancer, and some of them have been approved by the U.S. Food and Drug Administration (FDA) for HER2 testing in breast cancer since 1998.Although HER2 status can be directly tested by in situ hybridization (ISH), many laboratories have adopted IHC as a screening test, and FISH as a confirmation test for HER2 IHC equivocal cases, considering higher failure rate, longer procedure time and higher reagent cost of FISH, compared to that of IHC. Moreover, Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals m...

show abstract

Breast cancer biomarkers before and after neoadjuvant chemotherapy: does repeat testing impact therapeutic management?

Cited by 28 publications

References 29 publications

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer

Hormone- and HER2-receptor assessment in 33,046 breast cancer patients: a nationwide comparison of positivity rates between pathology laboratories in the Netherlands

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

Contact Info

Product

Resources

About