her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herceptin
 

Mod Pathol. 2010 Nov 19. [Epub ahead of print]
Semiquantitative hormone receptor level influences response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer.
Bhargava R, Dabbs DJ, Beriwal S, Yildiz IA, Badve P, Soran A, Johnson RR, Brufsky AM, Lembersky BC, McGuire KP, Ahrendt GM.
Department of Pathology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.
Abstract
Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in hormone receptor-negative/HER2+ tumors is seen in 27-45% of cases. In contrast, estrogen receptor (ER)+/HER2+ tumors demonstrate pathologic complete response in ∼8% of cases and is generally limited to weak-to-moderate ER+/HER2+ tumors. It is speculated that addition of trastuzumab to neoadjuvant chemotherapy regimen will increase the pathologic complete response rates in all HER2+ tumors. A list of HER2+ patients who received neoadjuvant chemotherapy (with trastuzumab) in the years 2007-2010 was obtained from our hospital database. The 104 HER2+ tumors were classified into three groups based on semiquantitative hormone receptor and HER2 results as follows: ERBB2 (ER-/PR-[H-score ≤10]/HER2+), Luminal B-HER2 Hybrid (LBHH; weak to moderate ER+ [H-score 11-199]/HER2+), and Luminal A-HER2 Hybrid (LAHH; strong ER+[H-score ≥200]/HER2+). Pathologic complete response was defined as absence of invasive carcinoma in the resection specimen and in the lymph nodes. Percentage tumor volume reduction was also calculated based on pretherapy size and detailed evaluation of the resection specimen. In all, 52% (25 of 48 cases) of ERBB2 tumors showed pathologic complete response, which was significantly higher than the pathologic complete response rate in LBHH (33%; 10 of 30) and LAHH (8%; 2 of 26) tumors. Average percentage tumor volume reduction was also highest in ERBB2 tumors (86%), followed by LBHH (74%) and LAHH (64%) tumors. We conclude that addition of trastuzumab to neoadjuvant chemotherapy regimen significantly increases the pathologic complete response rates in all HER2+ tumors. However, the benefit of trastuzumab is highest in ER-negative tumors and progressively decreases with increase in tumor ER expression. This information can be utilized to counsel patients considered for neoadjuvant chemotherapy and the same principle could be applied in the adjuvant setting.Modern Pathology advance online publication, 19 November 2010; doi:10.1038/modpathol.2010.209.
PMID: 21102420 [

Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
 

Hi Lani. Thank you once more for sharing such interesting findings.
I had neo adjuvant chemo. My tumor diminished during the 2 first FEC cycles and then stopped. I had imagery then before starting the 12 weeks of Taxol Herceptin. Imagery again after these cycles showed no benefit. I am 90% ER+ which is LAHH from what I understand. My onc fought to get me Lapatinib for a year a year of Herceptin hoping it would work better for me than herceptin. At the time we did not know that a combination of Herceptin and Lapatinib together may have been better. (may not be true for LAHH)
As you see 4 years later I have a liver met. What options are left for LAHH? Hormonotherapy alone is not enough. I figure it has to be combined with something. But what?
Thank you again Lani. I'll show this article to my onc.
Michka

Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
 

Thanks again Lani-as ever your posts extremely useful. Does this suggest that herceptin with an anti hormonal agent would have a better chance of effectiveness? My onc reluctant to add one in while I am on Abraxane as apparently there is some data about taxanes being less effective when taken with Tamoxifen.She is open to persuasion though.
Trish

Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
 

Thanks, Lani. Great article.

Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
 

I am assuming these study results can also be valuable to adjuvant chemo/herceptin?

Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
 

Sucky news for us triple positives.

Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
 

What I take from this is just substantiation of the previously demonstrated effect that chemotherapy is not the most effective treatment for hormone positive patients, and that adding Herceptin to it doesn't change that. A more revealing test of the efficacy of Herceptin in this population, IMO, would be treating highly hormone positive, Her2+ ("luminal A Her2+") patients with neoadjuvant endocrine therapy, with our without Herceptin.

Hopeful