MUST READ-- metastatic her2+ breast cancer not necessarily the death sentence it was

[Lani]

previously set out to be. There are Durable complete responses of Stage IV patients and this article set out to examine them. Shows how important it is to include herceptin in first line treatment of Stage IV and how important it is to continue it-- feel free to show this to governments/insurance companies who don't want to pay for herceptin!

From Annals of Oncology Ann Oncol. 2012 Jul 5. [Epub ahead of print]


Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer
G. Gullo1,*, M. Zuradelli2, F. Sclafani1, A. Santoro2 and J. Crown1
+ Author Affiliations

1Department of Oncology, St Vincent's University Hospital, Dublin, Ireland;
2Oncology and Haematology Unit, Humanitas Cancer Center, Rozzano, Italy
↵*(E-mail: g.gullo@svuh.ie)


Individual cases of prolonged complete response (CR) of HER2-positive metastatic breast cancer (MBC) have been reported following treatment with trastuzumab/chemotherapy, but the frequency of durable remission is unknown [1, 2].

We carried out a retrospective study of long-term outcome of all patients with HER2-positive MBC treated in our institutions with chemotherapy and trastuzumab before March 2007. All patients had histology-proven, HER2-positive (3+ on immunohistochemistry and/or HER2/neu gene amplification on FISH) breast cancer. None had received adjuvant trastuzumab.

Eighty-four patients were treated from May 2000 to March 2007 (Table 1). Thirteen (15%) achieved CR as defined according to RECIST 1.0 criteria [3]. As part of different institutional practices, patients in Dublin continued on trastuzumab until progression or at least for five years. In Milan trastuzumab was generally stopped in CR patients within two years of achieving remission. As of March 17, 2012, (median follow up 7 years, range 2.5–11.8 years), six of these patients remain alive and continuously cancer free at 142, 139, 122, 101, 84, and 84 months. Two additional patients are alive and continuously free of metastatic cancer at 107 and 105 months, having received curative locoregional therapy for new primary breast cancers. Five patients who achieved CR have developed relapsed MBC, at 44, 37, 35, 30, and 15 months, two while receiving maintenance trastuzumab (at 44 and 37 months, respectively). Three others had discontinued trastuzumab (21, 8, and 4 months after cessation).

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Table 1.
Characteristics of patients

All of the eight DCR patients received trastuzumab together with their first chemotherapy for metastatic disease. Five (63%) DCR patients had estrogen receptor (ER) negative disease, and five had metastases limited to liver. All but one received a taxane-containing regimen with trastuzumab (docetaxel and carboplatin-4 and single agent taxane-3).

The median duration of trastuzumab for CR patients in the two institutions was 67 months (range: 49 to 107+) in Dublin and 14 months (range 5–26) in Milan. Interestingly, although the frequency of CR was very similar in the two institutions (Milan 16% and Dublin 15%), the proportion of patients with DCR was higher in Dublin than Milan (11% versus 6%, respectively), prompting speculation that the duration of trastuzumab therapy might be important.

This is the first reported series of long-term follow-up of patients with HER2-positive MBC who achieved CR following chemotherapy and trastuzumab. Our data suggest that a meaningful minority of patients achieve very prolonged complete remissions. Although the small numbers and the retrospective nature of the study preclude definitive statistics, the data also suggest that the impact of trastuzumab might be greater in patients with ER-negative disease (14% DCR—an observation consistent with trials conducted in earlier stage disease [4, 5]) and possibly in those with metastases confined to the liver. Furthermore, the complete absence of DCR among patients who received trastuzumab with their second or subsequent chemotherapy for metastatic disease suggests that this agent should be a component of initial treatment. For patients with ER-negative disease who received trastuzumab with first line chemotherapy, the DCR rate is 16%.

At present we are conducting a comprehensive molecular and cytogenetic study of these patients' tumor samples to identify a subset of patients with HER2-positive MBC who are more likely to achieve DCR following chemotherapy plus trastuzumab.

We hypothesize that overtly HER2-positive MBC may be a potentially curable disease.



The authors declare no conflicts of interest.

© The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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references

↵ Beda M, Basso U, Ghiotto C, et al. When should trastuzumab be stopped after achieving complete response in HER2-positive metastatic breast cancer patients? Tumori 2007;93:491-492.
find it @ StanfordMedlineWeb of Science
↵ Maciá Escalante S, RodrÃ*guez Lescure Ã�, Pons Sanz V, et al. A patient with breast cancer with hepatic metastases and a complete response to herceptin as monotherapy. Clin Transl Oncol 2006;8:761-763.
find it @ StanfordCrossRefMedline
↵ Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organisation for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-216.
Abstract/FREE Full Text
↵ Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010;375:377-384.
find it @ StanfordCrossRefMedlineWeb of Science
↵ Baselga J, Bradbury I, Eidtmann H, et al. First results of the NeoALTTO Trial (BIG 01-06 / EGF 106903): a phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Cancer Res 2011;70:24. abstr S3–3.
find it @ StanfordWeb of Science

[JennyB]

wow this is great to read so many positive things happening lately it seems!!

Thanks Lani

[Bunty]

Thanks so much Lani for this report - good news! I reckon for those of you here who received Herceptin as adjuvant therapy (not for stage IV disease), the results of studies will be very promising.
Cheers Marie

[MJsHusband]

This article mentions Stage IV but these don't seem to be Stage IV statistics. "The median duration of trastuzumab for CR patients in the two institutions was 67 months (range: 49 to 107+) in Dublin...". Am I missing something? MJ got about 12 months of effectiveness from Herceptin before recurrence.

[Ellie F]

Thanks Lani
Really interesting research. The five year of herceptin keeps cropping up. I wonder if other chemos apart from taxotere would have the same lasting effect? I also wonder if the disease burden was a factor? Seems like the further research they are planning is very much needed
Ellie

[Lani]

Yes, MJs husband, you are missing something. These are not Stage IV statistics for all Stage Ivs treated everywhere, but just for Stage IVs treated in their two groups of patients ie, Dublin and Milan.

And even within those two groups the stats differ as the "institutional policy" was such that Stage IV patients in Dublin continued on trastuzumab until progression or at least for five years whereas in Milan, trastuzumab was generally stopped in CR patients within two years of achieving remission.

If you reread the abstract with that in mind, it makes more sense and is another piece of evidence that continuing herceptin beyond progression(and just adding things) is the way to go.

[Julie D]

Great news, very exciting!

[MJsHusband]

Thanks Lani. I always struggle to understand these articles. I really need a "conclusions" paragraph where they sum it all up and spoon feed it to me. I appreciate your reply. It makes sense to me now.

[jellybean]

Hi Lani,

Thanks very much for posting this. Would it be possible to post the full article, or at least the Table 1? If not, could you please send me a PM with the article. I am very interested in this study. I saw the abstract from ASCO, and this article has some more details. I tried to access the compete article, but it didn't seem to be available without paying a fee.

Thanks again!

JB

[Mtngrl]

Thanks, Lani! That's certainly a higher number than the 2 to 5% rate of DCR that usually gets tossed around.

[marvass]

Thanks Lani, this is very important in decisions whether to stop IV herceptin or not after metastasis of her2+...NEVER !!
Mario

[StephN]

Hope this is the first step in finding more about how some of us stage IV types CAN and DO achive a long complete response.

Marvass - I stopped Herceptin after nearly 8 years - in Dec of 2008. I knew it was a chance I was taking, and so far, so good. Prior to 2008, I thought I would take it for the rest of my life or until it was no longer working.

From what I glean from the article, I fit the response group with several factors like hormone negative, liver mets mainly, and getting Herceptin with a Taxane at stage IV diagnosis.

Hope the researchers keep winnowing down into the subgroups to see where patients fit and how best to treat them.

[marvass]

StephN, 8 years is long as though you took it forever! So if there were any cells left surely the herceptin had time to find them and destroy them.
Mario

I was diagnosed with liver mets from
the start but I received AC chemo first and then herceptin with taxotere. Does that mean I am not "potentially curable". Do you have to have received herceptin first?
Thanks

[Ellie F]

Dear unregistered
I think what Stephanie posted makes a lot of sense. The simple answer is they just don't know for certain who will achieve this long term response.i suspect more research from other centres will highlight more sub groups than we currently know about and more combos of chemo that can achieve it.
Ellie

[Rolepaul]

Ongoing research will continue. With an estimate one in nine women getting breast cancer, and one of those having HER+ cancer, the population is high enough to warrant companies to address this disease. If the population gets too small, it is harder to justify the investigational cost for an organization. If a treatment can be determined that is broad spectrum enough, ie pnencillin based treatment of infections, then the cost and ability to treat should continue to come down. This will make doctors and insurance companies be more willing to provide effective treatment. I will say that we have had exceptionally little pushback on anything, but our contribution has put a damper on what we can do as a couple.

The state of care for Herceptin positive patients can be looked at as we have gone from a slide rule to a hand held calculator. We need to move to I-phone 5s and Samsung Galaxy III in treatment. Be the research team for your personal health care. Your patient population is one.

Thank you Lani for your continued good work.