tamoxifen and Her2+ cancer

From the article Alaska Angel posted above.  Li is the author of the study:

While the study confirmed a strong association between long-term tamoxifen therapy and an increased risk of ER-negative second cancer, it does not suggest that breast cancer survivors should stop taking hormone therapy to prevent a second cancer, Li said.

"It is clear that estrogen-blocking drugs like tamoxifen have important clinical benefits and have led to major improvements in breast cancer survival rates."

Please keep in mind that while there is good evidence that tamoxifen decreases the chance of recurrence for the majority of HR+ women, including Her2+ women, Her2+ women who are not extensive metabolizers of tamoxifen should almost certainly not take it.  Also drugs that interfere with the metabolism of tamoxifen should not be taken with tamox. 

About AIB1.  It seems high AIB1 levels predict a high probability to responding to tamoxifen.

AIB1 is a predictive factor for tamoxifen response in premenopausal women

S. Alkner¹, P.-O. Bendahl¹, D. Grabau², K. Lövgren¹, O. Stål³, L. Rydén⁴, M. Fernö^1,* and on behalf of the South Swedish and South-East Swedish Breast Cancer Groups

¹ Department of Oncology, Clinical Sciences, Lund University
² Department of Pathology, Clinical Sciences, Lund University
³ Department of Oncology, Clinical and Experimental Medicine, Linköping University
⁴ Department of Surgery, Clinical Sciences, Lund University, Sweden

^*Correspondence to: Prof. M. Fernö, Department of Oncology, Clinical Sciences, Barngatan 2B:1, Lund University Hospital, SE 221 85 Lund, Sweden. Tel: +46-46177565; Fax: +46-46147327; E-mail: Marten.Ferno@med.lu.se

Background: Clinical trials implicate the estrogen receptor(ER) coactivator amplified in breast cancer 1 (AIB1) to be aprognostic and a treatment-predictive factor, although resultsare not unanimous. We have further investigated this using acontrolled randomised trial of tamoxifen versus control.

Materials and methods: A total of 564 premenopausal women wereentered into a randomised study independent of ER status. Usinga tissue microarray, AIB1 and ER were analysed by immunohistochemistry.

Results: AIB1 scores were obtained from 349 women. High AIB1correlated to factors of worse prognosis (human epidermal growthfactor receptor 2, Nottingham histological grade 3, and lymphnode metastases) and to ER negativity. In the control arm, highAIB1 was a negative prognostic factor for recurrence-free survival(RFS) (P = 0.02). However, ER-positive patients with high AIB1responded significantly to tamoxifen treatment (P = 0.002),increasing RFS to the same level as for systemically untreatedpatients with low AIB1. Although ER-positive patients with lowAIB1 had a better RFS from the beginning, this was not furtherimproved by tamoxifen (P = 0.8).

Conclusions: In the control group, high AIB1 was a negativeprognostic factor. However, ER-positive patients with high AIB1responded significantly to tamoxifen. This implicates high AIB1to be an independent predictive factor of improved responseto tamoxifen and not, as has previously been discussed, a factorpredicting tamoxifen resistance.

amplified in breast cancer 1, breast cancer, coactivator, estrogen receptor, prognosis, tamoxifen

Received for publication February 14, 2009. Revision received April 21, 2009. Accepted for publication April 21, 2009.

Some evidence that our tamoxifen is not killing us.   

Note that this study was done on tumors before herceptin was used as adjuvant therapy. 

Does hormone receptor (HR) positivity affect the prognosis in breast cancers with human epidermal growth factor receptor 2 (HER2) overexpression?

 
Sub-category:Prognostic Factors Category:Tumor Biology and Human Genetics Meeting:2009 ASCO Annual Meeting Abstract No:e22091 Citation:J Clin Oncol 27, 2009 (suppl; abstr e22091) Author(s):Y. Lee, J. Sohn, B. Park, H. Chung, C. Suh, S. Kim, J. Koo, J. Kim, H. Choi, Y. Kim; Yonsei University College of Medicine, Seoul, Republic of Korea; National Health Insurance Co. Ilsan Hospital, Goyang, Republic of Korea

Abstract:

Background: Biologically, there is an unclear issue about the role of HR positivity in HER2 positive breast cancer. These HER2(+)/ HR(+) pts were grouped into luminal B type apart from HER2(+)/ HR(-) pts in molecular profiling. However, from the clinical point of view, these pts have been categorized and been treated as either the only HER2(+) disease regardless of HR status or vice versa. Thus, we investigated the impact of HR status on clinical outcomes in HER2-overexpressed breast cancers. Methods: We retrospectively reviewed medical charts of HER2-positive breast cancer pts who underwent curative surgical resection from 1996 to 2001 in the Severance hospital, Korea. Demographic comparisons were performed by Chi-square tests. Tumor size, nodal stage, TNM stage, HR status, and adjuvant tamoxifen use were included in the Cox proportional hazards model. Results: Among the total 174 HER2-positive pts, HR (n=93) was positive in 53.5% (n = 93) and HR-positive tumors were more likely to be premenopausal (73% v 52%; P=0.01) and well- differentiated (grade 1or 2; 77% v 62%; P=0.04). There were no significant differences according to HR status in terms of tumor size, nodal stage, TNM stage, operation methods, and chemotherapy regimen. In these HER2-positive pts, the 5-year disease free survival (DFS) was longer in HR(+) pts than in HR(-) pts (DFS; 82.9% v 61.5%; P= 0.01). In a subset analysis, the 5-year DFS of HER2(+)/ER(+) pts without adjuvant tamoxifen (n=26) was not different from that of HER2(+)/ ER(-) pts (DFS; 57.7% v 61.5%; P= 0.32). However, the 5-year DFS of HER2(+)/ ER(+) pts with adjuvant tamoxifen was significantly prolonged compared with that of HER2(+)/ ER(-) pts (DFS; 91.5% v 61.5%; P< 0.001). In a multivariate analysis of DFS, tumor size and adjuvant tamoxifen use significantly affected DFS with an adjusted hazard ratio of 2.56 (95% CI, 1.2-4.9; P= 0.01) and 6.58 (95% CI, 2.8-20.3; P< 0.001), respectively. Conclusions: In an analysis of HER2-overexpressed breast cancer, the presence of HR itself did not affect the prognosis. However, most of the survival benefit seems to be driven from adjuvant tamoxifen therapy not the HR status itself.

Dx 8/2007, IDC, 1cm, Stage I, Grade 3, 0/3 nodes, ER+/PR-, HER2+

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