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R.B. · 09-15-2010, 09:14 AM

It seems the answers as usual are far form straight forward.

Understanding Resistance to Tamoxifen in Hormone Receptor–Positive Breast Cancer
Michaela J. Higgins1 and Vered Stearns1,a

1 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.

aAddress correspondence to this author at: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans St., CRB I, Rm. 145, Baltimore, MD 21231-1000. Fax 410-955-0125; e-mail vstearn1@jhmi.edu.

The first 300 words of the full text of this article appear below.

The selective estrogen receptor (ER)1 modulator tamoxifen has been used for more than 30 years to treat and, more recently, to prevent breast cancer. Unfortunately, even among patients with ER-positive tumors, the response achieved with tamoxifen treatment is variable. Recent years have seen a sharp increase in the number of studies suggesting that the efficacy and safety of anticancer therapies such as tamoxifen depend not only on tumor characteristics but also on characteristics of the host. It is probable that future prescribing of truly "personalized" treatment approaches for our patients will be determined after analysis of both sets of traits. This Perspective summarizes recent basic and translational studies of putative mechanisms of tamoxifen resistance.

Tumor Characteristics

Resistance to tamoxifen therapy may be intrinsic or acquired. Breast cancers that produce either ER or progesterone receptor (PR) have the potential to respond to tamoxifen; however, a proportion of ER-positive tumors are intrinsically resistant to the drug. Historically, metastatic breast cancer that is both ER and PR positive (suggesting that the ER is functional) has an approximately 80% rate of response to antihormonal therapy, whereas tumors that are ER positive but PR negative have lower response rates, approximately 40%. Tumors that do not produce ER or PR are not expected to respond to tamoxifen.

Investigators have proposed several mechanisms of intrinsic resistance, including cross talk with growth factor–signaling pathways and a balance of ER coregulators. In addition, alterations in epigenetic regulation may cause a lack of ER production or lead to the acquisition of resistance to hormone therapy.

Recently, breast tumor phenotypes have been further characterized with DNA microarrays, and such studies have identified 5 clinically distinct subtypes: luminal A, luminal B, ERBB2-amplified, basal-like, and normal breast-like. So-called luminal B breast cancers that are classically associated with amplification of ERBB22 [v-erb-b2 erythroblastic leukemia viral . . . [Full Text of this Article]

09-15-2010, 09:14 AM	#5
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	Re: struggling with my AI's(i hate them) It seems the answers as usual are far form straight forward. Understanding Resistance to Tamoxifen in Hormone Receptor–Positive Breast Cancer Michaela J. Higgins1 and Vered Stearns1,a 1 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD. aAddress correspondence to this author at: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans St., CRB I, Rm. 145, Baltimore, MD 21231-1000. Fax 410-955-0125; e-mail vstearn1@jhmi.edu. The first 300 words of the full text of this article appear below. The selective estrogen receptor (ER)1 modulator tamoxifen has been used for more than 30 years to treat and, more recently, to prevent breast cancer. Unfortunately, even among patients with ER-positive tumors, the response achieved with tamoxifen treatment is variable. Recent years have seen a sharp increase in the number of studies suggesting that the efficacy and safety of anticancer therapies such as tamoxifen depend not only on tumor characteristics but also on characteristics of the host. It is probable that future prescribing of truly "personalized" treatment approaches for our patients will be determined after analysis of both sets of traits. This Perspective summarizes recent basic and translational studies of putative mechanisms of tamoxifen resistance. Tumor Characteristics Resistance to tamoxifen therapy may be intrinsic or acquired. Breast cancers that produce either ER or progesterone receptor (PR) have the potential to respond to tamoxifen; however, a proportion of ER-positive tumors are intrinsically resistant to the drug. Historically, metastatic breast cancer that is both ER and PR positive (suggesting that the ER is functional) has an approximately 80% rate of response to antihormonal therapy, whereas tumors that are ER positive but PR negative have lower response rates, approximately 40%. Tumors that do not produce ER or PR are not expected to respond to tamoxifen. Investigators have proposed several mechanisms of intrinsic resistance, including cross talk with growth factor–signaling pathways and a balance of ER coregulators. In addition, alterations in epigenetic regulation may cause a lack of ER production or lead to the acquisition of resistance to hormone therapy. Recently, breast tumor phenotypes have been further characterized with DNA microarrays, and such studies have identified 5 clinically distinct subtypes: luminal A, luminal B, ERBB2-amplified, basal-like, and normal breast-like. So-called luminal B breast cancers that are classically associated with amplification of ERBB22 [v-erb-b2 erythroblastic leukemia viral . . . [Full Text of this Article]