HER2 Support Group Forums - View Single Post - WHY breast cancer treatment can never be "one size fits all"

Lani · 08-12-2012, 06:41 AM

I often seem to rattle on regarding why it is important to look at breast cancer subtypes, comparing breast cancer to a fruit salad where one should not compare apples, oranges, pineapple, guavas and passionfruits (now was;t that delicious!)

Here is a perfect example of the need not only for individual treatment of tumors, but of different treatment of two tumors which developed simultaneously in the same patient.

Mol Cancer Ther. 2012 Aug 9. [Epub ahead of print]
Discordant cellular response to pre-surgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification.
Balko JM, Mayer IA, Sanders ME, Miller TW, Kuba MG, Meszoely IM, Wagle N, Garraway LA, Arteaga CL.
Source
1Medicine, Vanderbilt University.
Abstract
We describe herein a patient presenting with bilateral ER+ breast tumors. The patient was enrolled in a clinical trial exploring molecular aberrations associated with hormone-refractory tumor cell proliferation. Short-term (2-week) hormonal therapy with the aromatase inhibitor letrozole substantially reduced proliferation as measured by Ki67 immunohistochemistry in one tumor, while the second was essentially unchanged. Extensive molecular and genetic workup of the two tumors yielded divergent lesions in the two tumors: an activating KRAS mutation in the responsive tumor, and an amplification of the FGFR1 locus in the treatment-refractory tumor. These findings provide an insight to possible mechanisms of resistance to antiestrogen therapy in ER+ breast cancers. First, they illustrate the necessity of clinically approved assays to identify FGFR1 gene amplification, which occur in ~5% of breast tumors and have been linked to antiestrogen resistance. It is quite possible that the addition of FGFR inhibitors to ER-targeted therapy will yield a superior antitumor effect and improved patient outcome. Second, they suggest that the role of activating mutations in RAS, although rare in breast cancer, may need to be explored in the context of ER+ breast tumors.
PMID: 22879364

08-12-2012, 06:41 AM	#1
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	WHY breast cancer treatment can never be "one size fits all" I often seem to rattle on regarding why it is important to look at breast cancer subtypes, comparing breast cancer to a fruit salad where one should not compare apples, oranges, pineapple, guavas and passionfruits (now was;t that delicious!) Here is a perfect example of the need not only for individual treatment of tumors, but of different treatment of two tumors which developed simultaneously in the same patient. Mol Cancer Ther. 2012 Aug 9. [Epub ahead of print] Discordant cellular response to pre-surgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification. Balko JM, Mayer IA, Sanders ME, Miller TW, Kuba MG, Meszoely IM, Wagle N, Garraway LA, Arteaga CL. Source 1Medicine, Vanderbilt University. Abstract We describe herein a patient presenting with bilateral ER+ breast tumors. The patient was enrolled in a clinical trial exploring molecular aberrations associated with hormone-refractory tumor cell proliferation. Short-term (2-week) hormonal therapy with the aromatase inhibitor letrozole substantially reduced proliferation as measured by Ki67 immunohistochemistry in one tumor, while the second was essentially unchanged. Extensive molecular and genetic workup of the two tumors yielded divergent lesions in the two tumors: an activating KRAS mutation in the responsive tumor, and an amplification of the FGFR1 locus in the treatment-refractory tumor. These findings provide an insight to possible mechanisms of resistance to antiestrogen therapy in ER+ breast cancers. First, they illustrate the necessity of clinically approved assays to identify FGFR1 gene amplification, which occur in ~5% of breast tumors and have been linked to antiestrogen resistance. It is quite possible that the addition of FGFR inhibitors to ER-targeted therapy will yield a superior antitumor effect and improved patient outcome. Second, they suggest that the role of activating mutations in RAS, although rare in breast cancer, may need to be explored in the context of ER+ breast tumors. PMID: 22879364