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Old 09-11-2015, 10:09 AM   #1
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Arrow Compiling Data on HER2 Brain Mets

Hi,

I've been collecting information about HER2 brain mets and prognosis, not so much for us to think that we are represented by their statistics, but to be able to use the data to communicate with our doctors and press for more aggressive treatment of HER2 brain mets. I will start compiling quotes and references here, feel free to add any that you have that might be useful.

-Ann
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.

Last edited by agness; 09-12-2015 at 07:41 AM.. Reason: Wanted better icon
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Old 09-11-2015, 10:24 AM   #2
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

My neuro-oncologist shared the ASCO 2011 Graded Prognostic Assessment for Brain Metastasis that includes breast cancer and breaks out HER2 positivity (no differentiation between hormonal status though).

The 2011 report used an original dataset spanned 1985-2007, so it predates Perjeta and some other more current treatments, plus some HER2 patients didn't receive Herceptin until it was made publicly available.

ASCO Graded Prognostic Assessment for Brain Metastases [Journal of Clinical Oncology, January 2012]
http://jco.ascopubs.org/content/30/4/419.full
Figure 1 includes the scoring table, midway are the patient characteristics. I scored 90-100 for KPS but you might need to consult with your oncologist about what that is for you; it has to do with functioning level versus impairments. You see which column your diagnosis falls into and then you use the prognositc factor to the right under the patient score (0,.5,1.0,1.5,2.0) to see what your final total and then there is a key at the bottom of the table for median survival.

This recent report on HER2 Brain mets using the above validates this scoring method.
Graded prognostic assessment (GPA) of HER2 positive breast cancer patients with brain metastases. [2015]
http://meetinglibrary.asco.org/content/145612-156
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 10:30 AM   #3
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

The dataset is slightly older but the results are slightly more favorable:

"Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2− lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2− and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions."

Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer
http://www.redjournal.org/article/S0...abstract?cc=y=
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 11:14 AM   #4
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

Leptomeningeal metastases in breast cancer

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623833

"HER-2 status does not appear to impact overall survival from LM, but treatment with trastuzumab was associated with a significantly longer time to the development of LM (15.2 versus 9.9 months)"

"Individual case reports and case series have shown that IT trastuzumab may have some activity in HER-2 positive breast cancer LM and is potentially well-tolerated"

"In the appropriate clinical context, findings suggestive of LM on MRI are adequate to initiate treatment of LM even in the absence of a positive CSF cytology"
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 11:15 AM   #5
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

Early-onset brain metastases in a breast cancer patient after pathological complete response to neoadjuvant chemotherapy. - PubMed - NCBI
http://www.ncbi.nlm.nih.gov/m/pubmed/24222158

"Physicians should be aware of the possibility of early brain metastases, and consider new treatment strategies to prevent brain metastases in high-risk patients who achieve pCR."
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 11:20 AM   #6
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

Breast cancer metastases to cerebellum.

http://meetinglibrary.asco.org/content/125957-144
[this predates the release of Perjeta]



"approximately 10% of [all] breast cancer (BC) patients develop metastases to cerebellum"


"Her2 over-expression was higher than expected (13/18;72,2%)"


" Majority (11/18; 61%), developed cerebellar metastases as a resectable, first metastatic site, and 73% (8/11) of these patients had Her2 3+ BC, treated with trastuzumab. Our results suggest that Her2 3+ BC has a greater propensity to metastasize to cerebellum than Her2 negative BC."
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 11:29 AM   #7
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study
http://www.breast-cancer-research.co...df/bcr2944.pdf
[2011, Breast Cancer Research] -- this predates Herceptin and Perjeta but the protein links is very interesting and might help with tissue genetic profiling.

" Luminal A cancers had a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases. Primary tumors that gave first rise to bone metastases expressed frequently estrogen receptor (ER) and SNAI1 (SNAIL) and rarely COX2 and HER2, tumors with first metastases in the liver expressed infrequently SNAI1, those with lung metastases expressed frequently the epidermal growth factor receptor (EGFR), cytokeratin-5 (CK5) and HER2, and infrequently progesterone receptor (PgR), tumors with early skin metastases expressed infrequently E-cadherin, and breast tumors with first metastases in the brain expressed nestin, prominin-1 and CK5 and
infrequently ER and PgR."


Breast cancer molecular subtype: HER2+/HR-
No. of patients: 36
No. of metastatic sites: 48
Bone: 14 (29.2)
Liver: 13 (27.1)
Lung: 11 (22.9)
Non-regional lymph nodes: 4 (8.3)
Skin: 4 (8.3)
Pleura: 0 (0.0)
Brain: 1 (2.1)
Other 1 (2.1
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 11:37 AM   #8
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

IRSA - Stereotactic Radiosurgery for Patients with Metastatic Brain Cancer
http://www.irsa.org/metastatic%20guideline.pdf

[May 2008, the latest version I could find]

"Lesions of the brain and leptomeninges account for 80% of intracranial metastases. The majority of brain metastases (approximately 80%) are located in the cerebral hemispheres. The cerebellum (10–15%) and brainstem (2– 3%) are less frequently involved."

"Patients treated with conventional open surgical resection without WBRT had a 46% risk of failure at the site of the resection in a randomized trial evaluating the role of WBRT after surgical resection. In subsequent studies patients were treated with SRS alone (without WBRT). These studies found excellent local control (70–80% at one year). Other published series of patients treated with SRS have demonstrated a risk of distant brain failure at one year, ranging from 43% to 57%. In general, the risk of new metastasis in patients with solitary tumors is approximately 37% (crude), but the actuarial risk is 50% at one year"

__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 11:37 AM   #9
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

Note that they are studying switching the order of treatment to radiation therapy first (SRS) and surgery second to see if they can help limit LM mets

"This Phase II trial will investigate the safety, tolerability, and effectiveness of changing the order of receiving radiation therapy for treating brain cancer and brain metastases. Normal procedure is to follow surgical removal of a brain metastases with stereotactic radio surgery. This trial reverses the order of these treatments in the hope that doing the radiation first will lower the risk of cancer spreading throughout the spinal fluid which covers the brain and spinal cord, causing leptomeningeal metastases. Patients with smaller brain metastases will start at a lower dose of radiation than those with larger brain metastases. To qualify for the trial patients must have brain metastases that can be removed by surgery. The metastases must be between 2 and 6 cm in size and no more than four in number."
Dose Escalation/De-escalation Study of Pre-operative Stereotactic Radiosurgery for Brain Metastases(RAD 1002)

https://clinicaltrials.gov/show/NCT01252797
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 12:16 PM   #10
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

The Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients with Breast Cancer and Brain Metastasis
[Poster from the 2011 ASCO Breast Cancer Symposium, similar to the first link but just about brain mets in BC]
http://meetinglibrary.asco.org/conte...erImg&poster=1
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 12:19 PM   #11
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

ASCO Clinical Practice Guideline: Disease Management in Advanced HER2-Positive Breast Cancer With Brain Metastases

http://www.ascopost.com/issues/july-...etastases.aspx

"On review of the available evidence, the ASCO expert panel concluded that the majority of the evidence was insufficient to inform evidence-based recommendations for a traditional ASCO clinical practice guideline.

Thus, the recommendations were developed by a multidisciplinary group of experts and reviewed by a consensus ratings panel including radiation oncologists, neurosurgeons, members of the ASCO Breast Cancer Guidelines Advisory Group, and others using a formal consensus process based on the best available evidence and clinical experience."
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-11-2015, 12:23 PM   #12
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

ASCO Guideline for Management of Brain Metastases From HER2-Positive Breast Cancer: An Important Framework

http://www.ascopost.com/issues/july-...framework.aspx
[2014]


"In the Breast Cancer Graded Prognostic Assessment, a prognostic scoring metric derived from a multi-institutional database of 400 breast cancer patients, the median overall survival was 17 months (95% confidence interval [CI] = 13–23) in HER2-positive patients with brain metastases3; significant prognostic factors were Karnofsky performance status, age, HER2 status, and the interaction between estrogen receptor and progesterone receptor status and HER2. Other large retrospective series have reported median survival as high as 23 months in these patients."

"These recommendations also highlight the areas of need for randomized trials of systemic agents in both newly diagnosed and recurrent brain metastases. Indeed, interpreting results from clinical trials and their applicability to patients has been a challenge, given the heterogeneous patient populations and variable endpoints across trials. Traditional cytotoxic agents have some activity in the brain,5 but have often required coordination with radiation and/or surgical interventions to obtain durable control. As systemic therapies improve and begin to include combinations of agents with penetration across the blood-brain barrier, the guidelines will also likely evolve to include more frequent use of chemotherapeutic regimens as a primary treatment modality for HER2-positive breast cancer brain metastases."
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-14-2015, 01:24 PM   #13
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

The use of sterotactic radiosurgery for brain metastases from breast cancer: who benefits most?
http://sharedresources.fredhutch.org...-benefits-most

"In all subtypes other than TNBC, SRS can provide meaningful control of BM even in the setting of multiple lesions and may be worth repeating for new lesions that develop metachronously."
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-18-2015, 11:06 AM   #14
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

May we all live long and NED that something like this might be considered a possibility for those of us treated for brain mets:

SMART syndrome: a late reversible complication after radiation therapy for brain tumours

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101343/

"We report on four patients with reversible clinical and radiological features occurring years after radiation for brain tumours, suggestive for the so called SMART syndrome (stroke-like migraine attacks after radiation therapy)."
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 09-28-2015, 08:32 AM   #15
Rolepaul
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Join Date: Jan 2012
Location: Boulder Colorado as of January 2013
Posts: 388
Re: Compiling Data on HER2 Brain Mets

My wife is part of the Intrathecal Herceptin study and I am one of the point people in getting this method of treatment at least looked at by physicians. I think the compilation of the studies would be worthwhile. They started at Northwestern, but were done in a few other locations in parallel. There were some individuals that contacted me to get information on how to progress in getting treatment. The overall information that I have on this is very promising. There are still less than 20 patients that have been treated.
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Old 09-28-2015, 09:14 AM   #16
agness
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Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

" surgical resection of parenchymal cerebellar metastases has purportedly resulted in subsequent development of LM. Resection of a supratentorial brain metastasis that violates the ventricular system also appears to increase the risks of developing LM"

"isolated meningeal involvement is no longer an exceptional site of relapse after chemotherapy for breast cancer, particularly when taxanes or trastuzumab are used, both of which penetrate poorly into the CSF"

"LM involvement is remains a relatively rare manifestation of HER2/neu positive tumors (3-5%) notwithstanding the observed increased incidence of parenchymal 2].[37,73,157,160,227] In breast cancer, the most common solid tumor to cause LM, risk factors of LM include an infiltrating lobular carcinoma and cancers negative for estrogen receptor (ER) and progesterone receptor (PR).[4,169–171,177,108,181] Triple negative status of breast cancer (HER2/neu negative; ER negative; PR negative) has been reported to be a risk factor of LM.[230] LM involvement is remains a relatively rare manifestation of HER2/neu positive tumors (3-5%) notwithstanding the observed increased incidence of parenchymal brain metastasis."

"the incidence of undiagnosed or asymptomatic LM may be 20% or more with many solid tumors as illustrated in autopsy series."

"An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected"

Carcinomatous meningitis: Leptomeningeal metastases in solid tumors
http://www.ncbi.nlm.nih.gov/pmc/arti...tid836011title
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 10-01-2015, 09:52 AM   #17
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Arrow Re: Compiling Data on HER2 Brain Mets

"Studies have consistently demonstrated that the risk of CNS involvement is high in patients with HER2-positive metastatic breast cancer. Incidence ranges from 15% to 55%, depending on length of follow-up and stringency of screening. Within the HER2-positive cohort, estrogen receptor (ER)-negative disease confers a greater risk than ER-positive disease. In a 3,000-plus patient cohort from a National Comprehensive Cancer Network database, women with ER-negative disease had a 63% increased risk over ER-positive patients, he said."

"compared to patients with triple-negative breast cancer, those with HER2-positive disease have a longer time from metastatic diagnosis to CNS relapse (approximately 1 year vs < 6 months), greater control of extracranial disease at the time of CNS relapse (50% vs rarely), and longer median overall survival from the time of CNS relapse (1–2 years vs 3–5 months). However, patients with triple-negative disease rarely die as a result of CNS progression alone, whereas up to 50% of those with HER2-positive disease do, he pointed out."

"Patients with HER2-positive disease who receive local therapy as the primary approach to CNS metastasis often develop progression over the ensuing months and years."

“Our treatment goals are to prolong survival, palliate neurologic symptoms, and prevent symptom progression. And we have to balance treatment-related toxicities with overall brain control and minimize the risk of ‘neurologic’ death—that is, death from the progression of the CNS metastases,” Dr. Winer said.

How to Approach the Problem of CNS Metastasis in HER2-Positive Patients
http://www.ascopost.com/issues/march...-patients.aspx
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 10-02-2015, 08:56 AM   #18
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

"With improved systemic control and prolonged survival, the incidence of brain metastases has increased, and CNS disease, often in the setting of well-controlled extracranial disease, is proving to be an increasingly important and clinically challenging cause of morbidity and mortality in patients"

"finding new treatments that target BM has not been prioritized, and nearly all clinical trials have excluded these patients. However, as patients live longer due to advances in human epidermal growth factor receptor-2 (HER2)-targeted and systemic therapy, it appears that the incidence of BM is increasing"

"Because trastuzumab does not cross the blood–brain barrier (BBB), the CNS serves as a sanctuary for metastatic disease in the setting of sustained extracranial control and improved survival."

"treatments for HER2-positive BM are a growing unmet clinical need deserving of dedicated clinical trials evaluating novel therapeutics and strategies"

"observational data suggest that HER2-positive cells may exhibit tissue tropism that cannot be explained by circulatory patterns"

"In trastuzumab-treated patients, median survival from diagnosis of CNS metastases has varied across studies, ranging from 12 to 25 months"

"Historically, BM trials have included patients with various solid tumors. There are few trials testing novel therapies specifically in breast cancer BM, and even fewer solely in patients with HER2-positive disease "

Emerging treatment options for the management of brain metastases in patients with HER2-positive metastatic breast cancer
http://www.ncbi.nlm.nih.gov/pmc/arti...960/#Abs1title
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 10-06-2015, 12:42 AM   #19
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

"We show that CED of TP-38 is well tolerated at effective doses and provides some encouraging radiographic responses. However, we also show that the potential efficacy of agents delivered by CED may be severely constrained by inconsistent and ineffective infusion in many patients."

Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors (2007)
http://m.neuro-oncology.oxfordjourna.../10/3/320.full
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
Old 10-06-2015, 12:54 AM   #20
agness
Senior Member
 
Join Date: Aug 2014
Location: Seattle, WA
Posts: 285
Re: Compiling Data on HER2 Brain Mets

http://m.neuro-oncology.oxfordjourna...7-0beacc753dc7

CNS Anticancer Drug Discovery and Development Conference White Paper (2015)

Abstract

Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. Following this concise review of the science and clinical aspects of new CNS anticancer drug discovery and development, we discuss, under the rubric “Accelerating Drug Discovery and Development for Brain Tumors,” further reasons why the pharmaceutical industry and academia have failed to develop new anticancer drugs for CNS malignancies and what it will take to change the current status quo and develop the drugs so desperately needed by our patients with malignant CNS tumors. While this White Paper is not a formal roadmap to that end, it should be an educational guide to clinicians and scientists to help move a stagnant field forward.
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
agness is offline   Reply With Quote
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