READ THIS: much to be THANKFUL FOR AMONG her2 + BC PATIENTS

[Lani]

Trastuzumab Prolongs Survival in HER2+ Metastatic Breast Cancer

NEW YORK (Reuters Health) Nov 24 - Treating HER-2 positive, metastatic breast cancer with trastuzumab significantly increased survival in a retrospective study, to the point were such women given the drug had higher survival rates than similar women with HER2-negative disease.

Senior author Dr. Sharon H. Giordano, from the University of Texas M.D. Anderson Cancer Center in Houston, and associates used a prospectively maintained database at that institution to analyze outcomes for 2091 women diagnosed with metastatic breast cancer of known HER2 status between 1991 and 2007. Median follow-up was 16.9 months (range 0 to 176 months).

As reported in an early release issue of the Journal of Clinical Oncology, most patients had HER2-negative disease (1782, 85.2%). Of the remainder, 191 (9.1%) had HER2-positive disease and received first-line trastuzumab, and 118 (5.6%) had HER2-positive disease but did not receive trastuzumab. Median age ranged from 48 to 52 years. Median cumulative time on trastuzumab was 11.6 months (range 0.23 to 68.2 months).

One-year overall survival was 86.6% in the HER2-positive trastuzumab group, 75.1% in the HER2-negative group, and 70.2% in the HER2-positive without trastuzumab group. Corresponding rates at 2 years were 63.2%, 54.9%, and 41.3%.

In a model adjusted for patient and tumor characteristics and year of diagnosis, women with HER2-positive disease who received trastuzumab had a 44% decreased risk of death compared with women with HER2-negative disease. They also had a 55% decreased risk during the first 2 years compared with HER2-positive patients not given trastuzumab.

These findings, Dr. Giordano and colleagues maintain, emphasize that "trastuzumab is now the standard of care among patients with HER2/neu-positive disease."

They note that optimal duration of trastuzumab treatment remains to be established, as well as the long-term effect of the agent on the incidence of central nervous system metastases.

"Regardless," the investigators conclude, "the introduction of trastuzumab into the treatment paradigm of women with HER2/neu-positive breast cancer is probably the most important breakthrough in the management of breast cancer seen this decade."

They add: "With the advent of other forms of targeted therapy currently under study, we are bound to see even more improvement in prognostic outcomes of women with breast cancer."

J Clin Oncol 2009.

[Midwest Alice]

"They note that optimal duration of trastuzumab treatment remains to be established, as well as the long-term effect of the agent on the incidence of central nervous system metastases."

Does anyone think Herception could cause brain mets?

Or is it still the problem of Herceptin crossing the blood brain b?

[Lani]

discussed in an article I already posted within the past 24 hours--

Blood brain barrier is preserved in her2+ brain mets but not
in basal or triple negative brain mets:
Cancer. 2009 Nov 20. [Epub ahead of print] Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer. Yonemori K, Tsuta K, Ono M, Shimizu C, Hirakawa A, Hasegawa T, Hatanaka Y, Narita Y, Shibui S, Fujiwara Y.
Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. BACKGROUND:: Generally, the blood-brain barrier (BBB) of brain metastasis was thought to be disrupted. METHODS:: We retrospectively performed immunohistochemical staining for glucose transporter 1 (GLUT1) and breast cancer resistance protein (BCRP) to evaluate the status of the BBB in resected brain metastases. Associations between expression of GLUT1 and/or BCRP and the immunohistochemical profiles of breast cancers, such as the statuses of hormone receptors, human epidermal growth factor receptor 2 (HER2/neu), and a basal-type marker (cytokeratin 5/6, HER1), were also analyzed. RESULTS:: The study included 29 breast cancer patients with brain metastasis who had undergone brain tumor resections. Among the 29 patients, there was no expression of GLUT1 and BCRP in the intratumor microvessels of 9 (32%) and 11 (38%) patients, respectively. There was no expression of both GLUT1 and BCRP in 8 patients (28%). The expression of GLUT1 was significantly associated with that of BCRP (P < .001). A positive correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of HER2/neu-positive breast cancer (P = .012), while a negative correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of triple negative or basal-type breast cancer (P = .014 and P = .003 for triple negative and basal- type, respectively). CONCLUSIONS:: Brain metastases of triple negative or basal-type breast cancers may often disrupt the BBB, whereas brain metastases of HER2/neu-positive breast cancer tend to preserve the BBB. Cancer 2010. (c) 2009 American Cancer Society.
PMID: 19937674

Evidence and speculation from these authors summarized below:
Although preclinical investiga- tions of whether triple negative breast cancer or basal-type cancer cells have a significant affinity to brain tissue remain inconclusive, triple negative breast cancer and basal-type breast cancers may have a different pattern of brain metastasis development and brain tissue affinity compared with HER2/neu-positive breast cancer. Patients with triple negative breast cancer are more likely to develop distant metastases earlier than non-triple negative breast cancer patients, develop brain metastases sooner, and have a shorter overall survival. Therefore, the present study suggests that the development of brain metastases of triple negative breast cancer and basal-type breast cancer may be more aggressive with the disruption of the BBB.
Although brain metastasis generally develops during
the late phase of breast cancer, HER2/neu-positive primary breast cancer has been known to develop brain metastasis as the initial site of recurrence, and it has a shorter brain metastasis-free survival period compared with other types of primary breast cancer. In a preclinical study, HER2/neu overexpression increased the meta-static outgrowth of breast cancer cells in the brain,suggesting that HER2/neu-positive breast cancer cellshave a great affinity to brain tissue. Generally, primarybrain tumors, such as high-grade gliomas, infiltratedeeply into the normal brain tissue where the BBB isintact. The present study revealed that the BBB waslikely preserved in brain metastases of HER2/neu-positive breast cancer; therefore, we speculate that HER2/
neu-positive breast cancer may develop brain metastases based on its potential affinity for brain tissue, enablingtumor cells to infiltrate the brain tissue across endothelial cells without requiring the disruption of the BBB during an early stage of disease. In an National Surgical Adjuvant Breast and Bowel
Project-B31 adjuvant chemotherapy trial for HER2/neu-positive patients, no significant difference in CNS metastasis as a first or subsequent
event was seen between a trastuzumab group and a control group. mab therapy does not increase the risk of CNS relapse; instead, their data suggested that the CNS acts as a sanctuary site for HER2/neu-positive metastases because of the inability of trastuzumab to cross the BBB.26 The present study may support this interpretation and these results of previous studies.

So it MAY be the affinity of the her2+ breast cancer cells and/or the fact they do not seem to be associated with disruption of the bloodbrain barrier with the latter perhaps responsible for what they call the "sanctuary effect"----rather than herceptin itself being the culprit

In fact, it does seem that those treated with herceptin do better overall , even with brain mets, than those who are not. It has been recommended to continue herceptin or other anti-her2 therapy in those with brain mets even though it may or may not have direct effects on the brain mets. An indirect effect, perhaps from keeping the other mets under control, is speculated.

Hope this helps

[freyja]

...so, in my research for deciding if I should take part in the Neratinib trial, I'm hearing that it does or "might" cross the BBB. Is that true? Also, I'm wondering if taking Neratinib in any way effects what other kinds of treatments you can have down the road? I'll be talking with the trial nurse at my treatment center soon, but would love some insight from y'all, too!
Love, Celeste