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Old 01-01-2016, 11:35 AM   #1
Lani
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Lightbulb T cells that recognize HER2 receptor may prevent HER2+ bc recurrence

PUBLIC RELEASE: 30-DEC-2015
T cells that recognize HER2 teceptor may prevent HER2+ breast cancer recurrence
UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE


PHILADELPHIA - Recurrence of HER2-positive breast cancer after treatment may be due to a specific and possibly cancer-induced weakness in the patient's immune system -- a weakness that in principle could be corrected with a HER2-targeted vaccine -- according to a new study from the Perelman School of Medicine at the University of Pennsylvania. Results of the study show that T cells from patients whose breast cancer had recently recurred showed far weaker response to the HER2 receptor protein, compared to T cells from patients whose breast cancer had not recurred over a long period following treatment. The study, published in JAMA Oncology this week, suggests that patients with HER2-positive breast cancer -- which accounts for roughly 20 percent of the 260,000 invasive breast cancers diagnosed in the US each year -- might someday undergo immune status monitoring with blood tests before, during and after treatment, to allow physicians to gauge the risk of recurrence, and possibly to reduce that risk with therapies that boost anti-HER2 immunity.

"We know that it's not a fixed immune defect, because we have several clinical trials open where we're vaccinating people and can restore anti-HER2 responsivity," said the study's senior author Brian J. Czerniecki, MD, PhD, the Rhodes-Harrington Professor in Surgical Oncology at Penn and the co-director of the Rena Rowan Breast Center at Penn's Abramson Cancer Center.

An Immune Marker for Recurrence Risk

Czerniecki and colleagues have been investigating the role of the immune system in breast cancer, and the potential of cancer vaccines, for most of the past two decades. Their most recent research has focused on the T-helper type 1, or Th1, immune response in cancer, in which 'helper' T cells mobilize killer cells to attack cancer-related targets.

In the new study, the Penn team, including first author Jashodeep Datta, MD, a general surgery resident and a member of the Czerniecki laboratory, isolated immune cells from 95 women with invasive HER2-positive breast cancer, and analyzed the cells' ability to mount a Th1 response against the HER2 growth factor receptor protein. HER2-positive breast cancer cells overexpress the HER2 receptor to help drive their rapid proliferation.

The team found that, by a standard measure, the cells from women with recently recurrent cancer that had not yet been re-treated had only about a tenth of the anti-HER2 responsivity compared to that seen in women whose HER2+ breast cancer had not recurred for at least two years following treatment.

Looking at anti-HER2 responsivity across all the patients, the researchers found that patients with the least amount of responsivity had experienced only 47 disease-free months after treatment, on average, compared to 113 disease-free months for the patients in with the most responsivity.

The low anti-HER2 responsivity seen in the women with recurrent cancer was not part of a broader immune suppression. "We detected no other immune deficit -- just the deficit in the anti-HER2 response," Czerniecki said.

The findings complement those from two other studies published earlier this year by Czerniecki and his colleagues. In one, the scientists found that the Th1 responsivity against HER2 tends to vary strikingly from high responsivity in cancer-free and early-stage HER2-positive breast cancer patients, to low responsivity in advanced HER2-positive breast cancer patients. In the other study, patients whose tumors shrank during standard pre-surgery drug treatment had much stronger anti-HER2 responsivity, compared to patients whose tumors responded less completely to that drug treatment.

How patients lose their anti-HER2 responsivity during the formation and growth of a HER2-positive tumor isn't yet clear. "The thinking is that the patient's anti-HER2 T cells somehow become exhausted and die or otherwise stop responding," Czerniecki said. "We're trying to determine the mechanism, but we already know that we can 'fill the tank' with vaccines to restore that specific responsivity to HER2."

In addition to conducting ongoing mechanistic studies and vaccine trials, Czerniecki says his team hopes to confirm the association between anti-HER2 responsivity and cancer recurrence risk in larger clinical trials that would track patients' immune status over time.

###

Other Penn co-authors of the study are Megan Fracol, MD, Matthew T. McMillan, BA, Erik Berk, PhD, Shuwen Xu, MD, Noah Goodman, MPH, David A. Lewis, BA, and Angela DeMichele, MD, MSCE.

The study was sponsored in part by the National Institutes of Health (R01 CA096997), Pennies in Action (http://www.penniesinaction.org), and the University of Pennsylvania Abramson Cancer Center Breast Cancer Translational Center of Excellence.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top 'Honor Roll' hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2014, Penn Medicine provided $771 million to benefit our community.

###

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
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Old 01-04-2016, 09:39 PM   #2
agness
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Re: T cells that recognize HER2 receptor may prevent HER2+ bc recurrence

Ya know, I think they should immunize all us HER2 gsls the second we get to NED. I understand that it takes best when the tumor burden is low and with concurrent Herceptin treatment. They know it's safe and we don't care about a multi-strain vaccine against multiple types of BC. A 40% chance that the University of Washington/Fred Hutch vaccine works is better than the four strains of HPV that that new vaccine might possibly prevent. No? Wouldn't you get it if you could? What if you knew it was shelf stable and well-tolerated for over 15 years of study? It doesn't seem right as our sisters fall.
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  • 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.
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Old 01-18-2016, 12:34 AM   #3
VDC
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Re: T cells that recognize HER2 receptor may prevent HER2+ bc recurrence

Does anyone know if Dr. Czerniecki's research is adequately funded? I heard through the grape vine that his research group was moving from UPenn and I was wondering what the motivation might be for leaving UPenn. And I'm curious what the move will mean as far as trial participants! I would assume moving a laboratory would involved down time for clinical trials. I"m hoping not! But suspect there will be a period during which no additional gals will be added to his trials. Anyone know?
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Old 01-18-2016, 08:22 AM   #4
spiritualabundance
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Re: T cells that recognize HER2 receptor may prevent HER2+ bc recurrence

I agree with Agness! If there is a chance, why aren't we all getting vaccinated. I'd be willing to be part of this trial. With my lymph nodes negative, margins clear, both breasts gone, and only 2 treatments left, my biggest fear is BY FAR, recurrence. I'd love to have a chance. How can we protest, insist, who do we email? How do we get attention?
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6/6/2015-Found a lump in my L breast at 45 years young.
6/12/2015-First u/s
7/2015-Mammogram and 2nd u/s (same day)
8/7/2015-Needle aspiration u/s biopsy. Doctor indicated looked malignant. (thanks doc!! the wait after that sucked)
8/20/2015-Diagnosed w ER+,PR+,HER2+ BC in L breast (now 46 years young.)
9/24/2015-Saw first surgeon, referred by oncologist. Great guy. Office staff not advocates.
10/12/2015-Met w Plastic Surgeon. Amazing doctor. Recommended not immediate due to chemo and 'just get the cancer out first' attitude. Will do recon with him after chemo is complete.
10/12/2015-Called first surgeon's office who told me that it's been too long since the first consult and will need to schedule another consult on 10/24 and then schedule surgery within 2-3 AFTER that date. (BITE ME)
10/12-Found a new surgeon.
10/15-Consulted with new FEMALE surgeon. She was AMAZING! Asked me if I wanted to do the surgery on Monday (in 5 days). Stunned and thrilled!!
10/26/15-Surgery for bilateral mastectomy, port placed, and 3 nodes removed for SNB. 3 drains installed.
10/28/15-home from the hospital to recover.
10/30/2015-Follow up with surgeon. Drains removed. Was told tumor was removed but had more than doubled in size from 1.3 to 2.9cm. 3 nodes removed, all negative. Healthy breast was clear but several suspicious areas on affected left breast. Looks to be Stage 2A. Oncologist appt next week.
11/5/2015-Follow up with oncologist. Planning to start chemotherapy (Herceptin, Taxotere, and Carboplatin together beginning November 30th). Very nervous about side effects, low white blood count, anemia, steriods, etc, etc, etc. I'm not usually one to medicate myself for anything. Not ready for this. Kinda scared.
11/30/2015 - Isaiah 41:10 today for sure. Today was my first day (round) of TCH chemo treatment. Before receiving the cocktail, I saw the doctor who delivered the news that my CT scans (abdomen, chest, and pelvis were all clear). Praise God!! Feeling okay right now after chemo, just a bit sleepy. We'll see how the Neulasta, along with the other effects, rear their lovely heads over the next few days. Prayers please, as always.
12/17/2015-Decided it was time to shave my head and face the music.
1/11/2016-Went in for 3rd treatment. UGG. Spoke to the doctor first. Asked him to reduce the Decadron. Agreed! From 10mg to 4mg dosage. YAY! It still worked and I was able to rest and live. Praise God. I jokingly told him if he felt like dropping some of my treatment, to feel free. Guess what?! He agreed! Agreed to drop my 6th treatment meaning that I now only have 2 left and in March I'll be able to begin the reconstruction process. Additionally, he agreed to schedule me for a brain MRI to just double check for any spread. Anxiously awaiting.
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Old 01-18-2016, 11:04 AM   #5
VDC
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Re: T cells that recognize HER2 receptor may prevent HER2+ bc recurrence

It isn't as simple as Agness implies. This particular vaccine is made from each individual's T cells. Those cells are collected via apheresis, treated and then injected back over the course of 6 weeks. They can't vaccinate everyone because there isn't the lab available to treat everyone's T cells. In fact, I've been accepted into the clinical trial but the lab can't take me at the moment because there isn't room. The lab can only treat so many women. There just isn't the lab space or the lab workers to accommodate any more.
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Old 01-18-2016, 05:38 PM   #6
Andrea Barnett Budin
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Re: T cells that recognize HER2 receptor may prevent HER2+ bc recurrence

It is my understanding that this works best in those without active cancer.

You must go off of tx for a minimum of 6 wks. Which if you have active tumors puts you in a highly vulnerable place. Tumors take advantage of your holiday. They multiply and grow and spread into other areas.

It all sounds wonderful but -- then there's that...
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'95 post-meno dx Invasive LOBULAR w/9cm tumor! YIKES + 2/21 nodes. Clear mammo 10 mnths earlier. Mastec/tram flap reconst/PORT/8 mnths chemo (4Adria/8CMF). Borderline ER/PR. Tamoxifen 2 yrs. Felt BLESSED. I could walk and talk, feed and bathe myself! I KNEW I would survive...

'98 -- multiple mets to liver. HER2+ 80%. ER/PR- Raging, highly aggressive tumors spreading fast. New PORT. 9 mnths Taxotere Fought fire w/fire! Pronounced in cautious remission 5/99. Taxotere weekly for 6 wks, 2 wks off -- for 9 mnths. TALK ABOUT GRUELING! (I believe they've altered that protocol since those days -- sure hope so!!)
+ good old Vit H wkly for 1st 3 yrs, then triple dosage ev 3 wks for 7 yrs more... The "easy" chemo, right?! Not a walk in the park, but not a freight train coming at 'ya either...

Added Herceptin Nov '98 (6 wks after FDA fast-tracked it for met bc). Stayed w/Vit H till July '08! Now I AM FREE! Humbly and eternally grateful for this life-saving drug! NED since '99 and planning on keeping it that way. To hell w/poor prognosis and nasty stats! STOPPED VIT H JULY '08...! REMAIN STABLE... Eternally grateful...Yes is a world & in this world of yes live (skillfully curled) all worlds ... (e e cummings) EVERY DAY I BEAT MY PREVIOUS RECORD FOR # OF CONSECUTIVE DAYS I'VE STAYED ALIVE. Smile KNOWING you too can be a miracle. Up to me and God now...
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