Receptor Status Change From Primary to Residual Breast Cancer After Neoadjuvant Chemotherapy and Analysis of Survival Outcomes

Parinyanitikul, Napa; Lei, Xiudong; Chávez-MacGregor, Mariana; Liu, Shuying; Mittendorf, Elizabeth A.; Litton, Jennifer K.; Woodward, Wendy A.; Zhang, Amy Hong; Hortobágyi, Gabriel N.; Valero, Vicente; Meric‐Bernstam, Funda; González-Angulo, Ana M.

doi:10.1016/j.clbc.2014.09.006

Cited by 34 publications

(21 citation statements)

References 28 publications

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“…Some reports have demonstrated that in a significant percentage of HR-positive tumors, exposure to taxane-based neoadjuvant chemotherapy causes a loss of ERα expression 14 . Therefore, we used western blotting assays to determine whether long-term exposure to paclitaxel caused changes in the expression levels of ERα in T47D PAC cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Effects of CDK4/6 Inhibition in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Cells with Acquired Resistance to Paclitaxel

Trapé¹,

Liu²,

Ueno³

et al. 2016

J. Cancer

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Among patients with hormone receptor (HR)-positive breast cancer, those with residual disease after neoadjuvant chemotherapy have a higher risk of relapse and poorer survival than those with a complete response. Previous studies have revealed a correlation between activation of cell cycle-regulating pathways in HR-positive breast cancer, particularly cyclin-dependent kinase (CDK) 4 and 6/cyclin D1 signaling, and resistance to standard therapies. Although CDK4/6 inhibition by palbociclib in combination with endocrine therapy has shown potent antiproliferative effects in HR-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, the potential role of palbociclib in re-sensitizing chemotherapy-resistant HR-positive breast cancer is not well defined. We hypothesized that CDK4/6 inhibition by palbociclib re-sensitizes HR-positive/HER2-negative residual breast cancer to taxane-based adjuvant therapy. Using cell counting, flow cytometry, and western blotting, we evaluated the efficacy of palbociclib alone and in concurrent or sequential combination with paclitaxel in parental and paclitaxel-resistant T47D HR-positive/HER2-negative breast cancer cells. The CDK4/6 pathway was constitutively active in both parental and paclitaxel-resistant T47D cells; thus, both cell types were highly sensitive to the inhibitory effects of single-agent palbociclib on cell growth and cell cycle progression. However, palbociclib did not re-sensitize resistant cells to paclitaxel-induced G2/M arrest and cell death in any of the combinations tested. Our results suggest that CDK4/6 inhibition by palbociclib does not re-sensitize HR-positive/HER2-negative residual breast cancer to chemotherapy. Nevertheless, the fact that CDK4/6 activation remained intact in paclitaxel-resistant cells indicates that patients who have HR-positive/HER2-negative residual disease after taxane-based neoadjuvant chemotherapy may still benefit from palbociclib in combination with other regimens, such as endocrine therapies, for adjuvant therapy.

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Section: Resultsmentioning

confidence: 99%

Effects of CDK4/6 Inhibition in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Cells with Acquired Resistance to Paclitaxel

Trapé¹,

Liu²,

Ueno³

et al. 2016

J. Cancer

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“…On the other hand, gain of hormone receptor expression after NAT is associated with significantly better outcomes, compared with patients with unchanged hormone receptor expression [ 45 , 46 ]. It has even been shown that the improvement on survival rates for patients with ER and PR expression gain is dependent on the magnitude of change [ 47 ], however, gain of hormone receptor expression is much less frequently reported [ 22 , 31 , 32 ]. In our study, no gain in ER status was observed in neither of the NAT-treated nor non-treated cases, whilst for PR, we observed gain of status in only two cases from the NAT-treated group.…”

Section: Discussionmentioning

confidence: 99%

Effect of neoadjuvant therapy on breast cancer biomarker profile

et al. 2020

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Background: Breast cancer clinical management requires the assessment of hormone receptors (estrogen (ER) and progesterone receptor (PR)), human epidermal growth factor receptor 2 (HER2) and cellular proliferation index Ki67, by immunohistochemistry (IHC), in order to choose and guide therapy according to tumor biology. Many studies have reported contradictory results regarding changes in the biomarker profile after neoadjuvant therapy (NAT). Given its clinical implications for the disease management, we aimed to analyze changes in ER, PR, HER2, and Ki67 expression in paired core-needle biopsies and surgical samples in breast cancer patients that had either been treated or not with NAT. Methods: We included 139 patients with confirmed diagnosis of invasive ductal breast carcinoma from the Colombian National Cancer Institute. Variation in biomarker profile were assessed according to NAT administration (NAT and no-NAT treated cases) and NAT scheme (hormonal, cytotoxic, cytotoxic + trastuzumab, combined). Chisquared and Wilcoxon signed-rank test were used to identify changes in biomarker status and percentage expression, respectively, in the corresponding groups. Results: We did not find any significant variations in biomarker status or expression values in the no-NAT group. In cases previously treated with NAT, we did find a statistically significant decrease in Ki67 (p < 0.001) and PR (p = 0.02605) expression. When changes were evaluated according to NAT scheme, we found a significant decrease in both Ki67 status (p = 0.02977) and its expression values (p < 0.001) in cases that received the cytotoxic treatment. Conclusions: Our results suggest that PR and Ki67 expression can be altered by NAT administration, whereas cases not previously treated with NAT do not present IHC biomarker profile variations. The re-evaluation of these two biomarkers after NAT could provide valuable information regarding treatment response and prognosis for breast cancer patients.

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“…Change in HR and HER2 status after NAC is a well-known phenomenon in BC, occurring in 10-30% of cases [8,9]. Although the older results might be affected by pre-analytical and analytical pitfalls [10,11], a real biological heterogeneity may be implied.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer

et al. 2017

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Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. Materials and Methods: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions. Results: Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation. Conclusions: The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.

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Receptor Status Change From Primary to Residual Breast Cancer After Neoadjuvant Chemotherapy and Analysis of Survival Outcomes

Cited by 34 publications

References 28 publications

Effects of CDK4/6 Inhibition in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Cells with Acquired Resistance to Paclitaxel

Effects of CDK4/6 Inhibition in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Cells with Acquired Resistance to Paclitaxel

Effect of neoadjuvant therapy on breast cancer biomarker profile

Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer

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