Jean, Alaska Angel et al-- stats for difference herceptin makes for small <2cm her2+

[Lani]

breast cancers--reposted due to silly typo in title of previous thread

Follow-up still shorter for those getting herceptin, so must wait for 4,5,6 year results to be sure herceptin did not just delay recurrence. Will try to read and check if all got chemo concurrently with herceptin



Cancer. 2011 Jun 16. doi: 10.1002/cncr.26171. [Epub ahead of print]
Adjuvant trastuzumab with chemotherapy is effective in women with small, node-negative, HER2-positive breast cancer.
McArthur HL, Mahoney KM, Morris PG, Patil S, Jacks LM, Howard J, Norton L, Hudis CA.
Source
Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York. mcarthuh@mskcc.org.
Abstract
BACKGROUND:
Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node-negative HER2-positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single-institution, sequential cohort study of women with small, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted.

METHODS:
Women with ≤2 cm, node-negative, HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization ≥2) breast cancer were identified through an institutional database. A "no-trastuzumab" cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004 and a "trastuzumab" cohort of 155 trastuzumab-treated women diagnosed between May 16, 2005 and December 31, 2008 were described. Survival and recurrence outcomes were estimated by Kaplan-Meier methods.

RESULTS:
The cohorts were similar in age, median tumor size, histology, hormone receptor status, hormone therapy, and locoregional therapy. Chemotherapy was administered in 66% and 100% of the "no trastuzumab" and "trastuzumab" cohorts, respectively. The median recurrence-free and survival follow-up was: 6.5 years (0.7-8.5) and 6.8 years (0.7-8.5), respectively, for the "no trastuzumab" cohort and 3.0 years (0.5-5.2) and 3.0 years (0.6-5.2), respectively, for the "trastuzumab" cohort. The 3-year locoregional invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival were 92% versus 98% (P = .0137), 95% versus 100% (P = .0072), 82% versus 97% (P < .0001), and 97% versus 99% (P = .18) for the "no trastuzumab" and "trastuzumab" cohorts, respectively.

CONCLUSIONS:
Women with small, node-negative, HER2+ primary breast cancers likely derive significant benefit from adjuvant trastuzumab with chemotherapy. Cancer 2011;. © 2011 American Cancer Society.

Copyright © 2011 American Cancer Society.

PMID: 21681735 [PubMed - as supplied by publisher]

Concluding comment in the article:
Although we lack, and are unlikely to ever obtain, randomized data addressing the role of trastuzumab in women with small, node-negative, HER2þ primary inva- sive breast cancers, our study suggests that these women have excellent outcomes after adjuvant chemotherapy with trastuzumab compared with a similar population of trastuzumab-untreated women. The critical issue is that approximately 10% of the approximately 200,000 new cases of invasive breast cancer anticipated in the United States in 201116 will be otherwise low risk but HER2þ is associated with an estimated 20% 5-year recurrence risk.3-5 Therefore, if our results are correct, broad use of trastuzumab with chemotherapy in this under- studied population would have an important public health impact. Our data support consideration of adjuvant trastuzumab-chemotherapy for women with small, node-negative, HER2 positive breast cancer.

[1rarebird]

Thank you, Lani--These data are impressive and although they are likely only applicable for females in the two cohorts evaluated, I am going to apply them to me none the less. I like giving my long-suffering wife some good news from time to time.--bird

[Laurel]

Hey, Bird, you are welcome to join us "hens" on the good-news-stats roost! We'll budge over for ya.

[AlaskaAngel]

Thanks for this interesting post, Lani.

What I have to say isn't "proof" by any means, and is just meant to encourage further thought and perhaps even investigation.

What percentage of HER2 positive bc occurs in those who are older (45+ years old, perimenopausal/menopausal/postmenopausal) versus those who are younger (<45, premenopausal) and how does that effect the usefulness of adding chemotherapy in each of these two groups in regard to the results of that study? My sense is that the majority of HER2/neu positive patients are young, and that the authority of the study should be questioned in terms of the effectiveness of chemotherapy in addition to the trastuzumab when used in older patients, so that the results of the majority are not assumed to be the same for a minority group.

I know there is no data for that question, but somehow that question needs to be posed if the study results are going to be truly meaningful. There is little or no information about it because this patient group not only was largely not included in the clinical trials using chemotherapy and trastuzumab, but because there is such an appalling paucity of information about the use of traztuzumab alone for any patient group.

In addition, for those age 45 and older who become postmenopausal as a result of the use of chemotherapy, what is the added recurrence rate for them due to significant weight increase due to the use of steroids added in support of the chemotherapy, as well as any increased weight gain following chemotherapy because of the lowering of testosterone in addition to the arthraltias involved with the aromatase inhibitors prescribed after chemotherapy -- in comparison to those who are given trastuzumab alone, perhaps including ovarian ablation by other means that do not require the use of steroids to produce menopause?

I suspect that the primary effect that chemotherapy has in reducing recurrence/metastasis is that it brings on earlier or more complete menopause, and the main benefit of that is that menopause slows down metabolism at the cellular level, which then reduces cell division, which allows more opportunity for normal cell differentiation, more opportunity for proper cell apoptosis to occur, and slower progression to recurrence.

The counter effect to that is that slow metabolism in combination with the support steroids that is required for chemotherapy use decreases the proportion of body muscle and increases the proportion of body fat, which increases the amount of body inflammation. The change in body make-up takes time, which is why recurrence continues to occur late for those who are not fat or are somewhat younger (perimenopausal) at time of diagnosis. Those who are younger do not reach complete menopause as easily and tend to recur earlier.

The study unfortunately does not answer the key question: What group might benefit from trastuzumab used alone, that is actually having a higher recurrence rate due to adding chemotherapy with the support drugs required for that?

Alaska Angel

[tricia keegan]

Thanks Lani, I had positive nodes so looking forward to some good data/news from that area!!!

[suzan w]

Interesting post, Lani. I printed it so I could study it more (maybe with a dictionary near!!!) xo Suzan W

[Jean]

Lani, thank you for thinking of me and posting the informative and intersting study. We know that HER2 is associated with an estimated 20% 5-year recurrence risk. That back in 05 many early stage women advanced to later stage HER2. While others did not...would be great if the lab rats could find out what that code is. As more data becomes available we will gleen more answers and of course treatment will change. We also know that the risk of developing breast cancer increases as we get older. About 1 out of 8 invasive breast cancers are found in women younger than 45, while about 2 out of 3 invasive breast cancers are found in women age 55 or older.

There is a strong correlation between lack of physical activity and obesity. A recent study from the Women’s Health Initiative found that physical activity among postmenopausal women who walked about 30 minutes per day was associated with a 20 percent reduction of breast cancer risk. However, this reduction in risk was greatest among women who were of normal weight. For these women, physical activity was associated with a 37 percent decrease in risk.

While we do all we can via life style and treatment there will always be risk factors we cannot control.
Dense breasts, race and ethnicity, our enviorment, exposure to toxins...etc.

There is a trial being conducted with just herceptin.
It will be interesting to hear about that data when it is available.

The path trastuzumab has taken is a demonstration of how progress is made. Treatment changes as evidence accumulates and new knowledge is acquired. However, the path is also a demonstration of how slow and tedious the process can be. The problem is in not knowing if and how trastuzumab will benefit different groups of patients. In the meantime I am happy to read this data that you provided....as it shows we are seeing progress!

Once Again, Thank you Lani.
jean

[snolan]

Thanks for the post. I was dx at age 41 w stage 1 Her2+ and have found it frustrating when doing research that most of what I find has to do with more advanced stages. Makes it hard to compair results ,especially since I am only 1 yr out I still have those what if fears. Good to see some positive result figures to calm my nerves.