Jan 23, 2012 02:00PM voraciousreader wrote:
Beesie... Minnshark's is .4 Grade 3.
Posted on: Jan 21, 2012 02:05PM
Posted on: Jan 21, 2012 02:05PM
Curious... my step mom had BMX due to high grade DCIS in left and suspicious area of concern in right. After surgery, pathology came back with invasive ILC Her2+ in right breast. Very small, less than 1/2 cm. Sentinel nodes were clear. Surgeon thought no chemo would be needed. I thought all Her2+ invasive tumors were treated with chemo and herceptin. What size warrants chemo and herceptin?
Jan 23, 2012 02:00PM voraciousreader wrote:
Beesie... Minnshark's is .4 Grade 3.
Jan 23, 2012 02:22PM Minnshark wrote:
Thank you. Breathing a little easier now, but I have another question. It was IDC .4, grade 3, ER/PR-, HER2 neu 3+. No node involvement. Staged at 1a. How big a deal is HER2 3+ vs HER2+. Dumb question but should I be more concerned. I felt (and continue to feel) confident that both of my opinions agreed no chemo based on my situation, but I think I have to be more diligent than ever before in my follow ups and tracking of my own symptoms. I feel like a hypochondriac already.
Jan 23, 2012 02:35PM lago wrote:
Minnshark You got 2 opinions, one from the Mayo clinic (rated #4 in the US for cancer treatment) that agreed you didn't need further treatment. It's tough to understand because like you said most HER2+ tumors are much larger and also in the nodes. What your doctors are saying is the risks of getting chemo/hercptin out-weight the risks of mets. There is not crystal ball but the odds are in your favor of not needing it. Doctors do not like to over treat.
I'm an oddball because I have this large tumor (6.5cm IDC+DCIS, 5.5cm IDC only) and didn't have node involvement. Us oddballs do happen… and I'm not complaining about being an oddball this time!
Jan 23, 2012 03:08PM Minnshark wrote:
Thank you. I felt real confident in my decision until I came to the forums and started reading. I have taken a deep breath and have strengthened my resolve to stay on my path.
I am very lucky to live as close as I do to the Mayo Clinic and to have the resource available to me.
Jan 23, 2012 04:17PM beesie.is.out-of-office wrote:
VR, I posted the recurrence risk numbers that I did because there seemed to be so many numbers flying around here about Stage I HER2+ recurrence risk and I wanted to show that everyone was probably right. There is no one number that defines with the risk is - for Stage I HER2+ breast cancer, it can actually range from under 2% to over 32%, depending on other pathology factors. What that also means is that we should never assume that the risk number that we've been told applies to anyone but us. And we should always take what we read - either here or anywhere on-line or in any BC book - with a grain of salt. Every cancer is different. The numbers that we read or hear about recurrence risk might be correct as an average for all women with a particular diagnosis but we are all unique and not average. By the way I did put Minnshark's data into the CancerMath form and came up with the same 8.1% recurrence risk that you noted.
Minnshark, I'm glad that you are feeling more confident about your decision. This board is a wonderful resource but sometimes it's easy to be frightened by things that we read here. Most of us know little or nothing about breast cancer when we are diagnosed (that was me 6 years ago) and don't realize that some seemingly small differences in diagnosis can make a significant difference in outcomes and treatment decisions. (((Hugs))) to you.
Jan 23, 2012 04:34PM voraciousreader wrote:
Beesie... Also... It is always a good idea to look at several years of NCCN guidelines to look at the trends. In light of last week's announcement in the Lancet regarding HER2 positive tumors, it wouldn't surprise me if the guidelines are updated. As I mentioned to you, when I was diagnosed, I thought the guidelines for my type of breast cancer was a moving target. Everyone needs to make their decision based on the best evidence when they are diagnosed and then join the rest of the sisters in making a decision and moving on with living....
Jan 23, 2012 05:31PM bluedasher wrote:
Iago, the 25% number matches what was found in the MD Anderson retrospective study of cancers smaller than 1 cm that had no treatment with chemo and no Herceptin. The study results were presented at the 2008 San Antonio Breast Cancer Symposium. The study covered 965 US patients and 350 cases from Europe. Patients had been diagnosed with node negative tumors less than 1 cm between 1990 and 2002 so they had 5 year recurrence data on them. 10% of the group was HER2+.
For the HER2+ group, 5-year disease free survival was 77% = slightly better than 25% recurrence. More striking to me, their 5-year distant recurrence free survival was 86.5% = ~15% had distant recurrences. For triple negative, these numbers were 85.2% and 95.6%. For HR positive HER2-, the numbers were 95.2% and 97.5%.
So about 1 in 4 had recurrences and about 1 in 6 had distant recurrences.
Bessie and voraciousreader, how are you getting recurrence numbers from CancerMath? I can only find survival estimates on CancerMath.net - not recurrence predictions. In any case, the site produces the same numbers that it did when I first looked at it before the MD Anderson study came out. I don't think that they have updated their mathematical models to adjust for the higher recurrence of early stage HER2+ that was found in the MD Anderson study.
ccjj, I think that tumors less than 0.5 are considered to be in the grey area for whether they should have chemo and Herceptin. The MD Anderson study didn't break out the numbers for less than 0.5 cm and 0.5 to 1 cm. My impression is that few HER2+ cancers are caught early enough to be under 0.5 cm so there isn't a lot of data but there is some indication that the recurrence is much less for those than the over 0.5 cm.
Minnshark, as I understand it, HER2 + and HER2 +++ or HER2 3+ mean the same thing. One test for HER2 gives a number between 1 and 3 that indicates the amount of cells that have the extra receptors. If the number is 3, they sometimes write that as HER2 +++ or HER2 3+ but it means that the tumpr is definately HER2 +. If it is between 2 and 3, they might do another more accurate test to determine HER2 status.
Jan 23, 2012 05:50PM lago wrote:Thanks bludasher Was there a breakdown of HER2+ hormone positive and HER2+ Hormone negative?
Jan 23, 2012 06:04PM voraciousreader wrote:Trastuzumab May Benefit Patients with Very Small & Low-Grade Breast Tumors
Oncology Times . 31(4) Clinical Spotlight Supplement:2-4, 25 February 2009.
SABCS Abstracts 701 and 702
Adjuvant systemic therapy with the anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab (Herceptin) should strongly be considered in early-stage breast-cancer patients with very small and low-grade HER2-positive tumors, researchers reported at the San Antonio Breast Cancer Symposium.
A US team came to that conclusion after finding that HER2 positivity is a powerful negative prognostic factor for patients with node-negative disease and tumors that are 1 cm or smaller. In addition, UK researchers found that HER2 positivity is associated with an increased risk of death due to breast cancer in patients with node-negative, histological Grade 1 or Grade 2 disease.
Together, the studies show that patients who are traditionally defined as low risk, but who are HER2-positive, have a poor prognosis. This is important because it tells us that HER2 status has a prognostic role even in low-risk tumors, said Angelo Di Leo, MD, PhD, Head of the Sandro Pitigliani Medical Oncology Unit and Chair of the Department of Oncology at the Hospital of Prato, Tuscany Cancer Institute, in Italy. Dr. Di Leo moderated the well-received, early-morning oral poster discussion of both studies.
Physicians need to consider offering these women Herceptin-based therapy in the adjuvant setting, said the senior investigator of the US team, Ana M. Gonzalez-Angulo, MD, MSc, Assistant Professor of Medicine in the Departments of Breast Medical Oncology and Systems Biology at the University of Texas M. D. Anderson Cancer Center.
The number of patients diagnosed with HER2-positive tumors 1 cm and smaller continues to increase as breast cancer surveillance and early-detection methods become increasingly sophisticated, she said.Article Outline | Back to Top Current Guidelines
Current treatment guidelines do not recommend that trastuzumab be given to women with HER2-positive tumors smaller than 0.5 cm and suggest only that clinicians discuss trastuzumab treatment with women whose tumors are 0.5 to 1 cm in size. The reason, Dr. Gonzalez-Angulo explained, is because these women were largely excluded from the definitive trials confirming the benefit of the drug.
Five randomized, Phase III clinical trials reported significant improvement in disease-free and overall survival with trastuzumab administered in conjunction with adjuvant chemotherapy for early-stage HER2-positive breast cancer. However these studies included principally node-positive cases, and four trials excluded patients with tumors 1 cm or smaller that were node-negative.
As a result, available data on the risk of recurrence in women with very small, node-negative tumors are limited, she said.
To help fill in the knowledge gap, Dr. Gonzalez-Angulo, Ronjay Rakkhit, MD, Chief Fellow in the Department of Oncology at M. D. Anderson and the study's first author, and colleagues used the center's Breast Cancer Research Database to evaluate the risk of recurrence in women with Stages TIa and TIb, node-negative, HER2-positive breast cancer.
A total of 965 patients with node-negative invasive breast tumors 1 cm or smaller were included in the analysis. Patients whose receptor status could not be analyzed and/or had received adjuvant chemotherapy or trastuzumab were excluded.
Ten percent of the patients had HER2-positive tumors, defined as gene amplification on fluorescence in situ hybridization (FISH) and/or overexpression of three or more receptors, with strong membranous staining in at least 10% of cells, on immunochemistry.
In addition, 77% of patients were hormone-receptor positive, and 13% were triple receptor-negative-that is, estrogen receptor-negative, progesterone receptor-negative, and HER2-negative. Women with triple receptor-negative disease face a particularly poor prognosis.
The median age of the patients at diagnosis was 57. Two thirds had Stage TIa disease, and the rest had Stage TIb.
To validate the findings, a second cohort of 350 cases with the same inclusion criteria and similar follow-up time were obtained from collaborators at the General Hospital Leoben in Austria and Institute Jules Bordet in Brussels.Article Outline | Back to Top US Study Results
Results of the M. D. Anderson dataset showed that the five-year, recurrence-free survival rate in women with HER2-positive tumors was 77% vs 94% in women with HER2-negative tumors.
In multivariate analysis, this translated into a significant 2.68 times higher risk of recurrence in patients with small HER2-positive tumors, compared with patients with small HER2-negative tumors, Dr. Gonzalez-Angulo reported.
The five-year distant recurrence-free survival rate was 86% in women with HER2-positive tumors, compared with 97% in women with HER2-negative tumors. This corresponded to a 5.3 times higher risk of distant recurrence in patients with HER2-positive tumors in the multivariate analysis.
In addition, women with HER2-positive tumors had 5.1 times the risk of recurrence and 7.8 times the risk of distant recurrence, compared with women with hormone receptor-positive tumors.
There was no significant difference in the risk of recurrence or distant recurrence in patients with Stage TIb vs Stage TIa disease.
As expected, women with triple-negative tumors were at particularly high risk of recurrence, Dr. Gonzalez-Angulo added. These women had a five-year recurrence-free survival rate of 85%, and a five-year distant recurrence-free survival rate of 96%.
The European subset confirmed the M. D. Anderson findings and showed reproducibility, she said. The five-year, recurrence-free survival rate in women with HER2-positive disease was 87%, compared with 97% in women with HER2-negative tumors, a significant difference.
Funding for the study was provided by the American Society of Clinical Oncology, the National Cancer Institute, and the Nellie B. Connally Breast Cancer Research Fund.Article Outline | Back to Top UK Study
For the UK study, University of Glasgow researchers sought to determine the number of patients both who were eligible for and who actually received trastuzumab therapy for early-stage breast-cancer at their institution in 2006. They also performed a retrospective analysis of the impact of HER2 status on survival of low-grade, node-negative HER2-positive patients who would currently be deemed ineligible for trastuzumab treatment.
For the first part of the study, data for all 951 patients diagnosed with early-stage breast cancer in 2006 were recorded prospectively in a database.
A total of 110 of the women had HER2-positive tumors, 57 (52%) of whom received trastuzumab therapy. Of the 53 (48%) patients who did not receive trastuzumab, 25 (43%) were considered to be at low risk of recurrence due to small, node-negative, low-grade tumors, reported Sian M. Tovey, MD, a Clinical Lecturer in the Section of Surgical and Translational Research at Glasgow Royal Infirmary.
Then, the researchers retrospectively analyzed a cohort of 367 women diagnosed with Grade 1 or 2, node-negative disease between 1980 and 2002. A total of 89% of cases were estrogen-receptor positive, and 72% had tumors smaller than 20 mm. Ten percent received chemotherapy, and 91% received endocrine therapy.
The five-year breast cancer-specific survival rate was 96% in the 348 women with HER2-negative disease, compared with 68% in the 19 women with HER2-positive disease. This translated to a significant 6.8 times higher risk of dying of breast cancer for women with low-grade, HER2-positive vs HER2-negative disease, Dr. Tovey reported.
This reduction in survival in HER2-positive cases persisted when patients were split into subgroups by estrogen-receptor status, tumor size-20 mm or greater versus less than 20 mm-and age-under 50, 50 to 65, and over 65 years, she said.
What this means is that no HER2-positive patient should be considered low risk. It's the biology of the tumor, not the grade or size, that matters. HER2-positive tumors are known to be aggressive, with poor differentiation and a high proliferation rate.
They should all be considered for Herceptin therapy, she continued, adding that the findings are already changing practice at her institution.Article Outline | Back to Top Uniform Praise
The research was uniformly praised by clinicians and researchers, many of whom crowded around the posters prior to the discussion session.
Dr. Di Leo noted that in the Herceptin in Adjuvant Breast Cancer (HERA) and National Surgical Adjuvant Breast and Bowel Project B-31 (NSABP B-31) trials, the benefit of trastuzumab seemed to be independent of disease stage. One could therefore speculate that trastuzumab would help patients with very small and/or low-grade tumors who are currently not being routinely treated, he said.
Minetta C. Liu, MD, Assistant Professor of Medicine in the Division of Hematology/Oncology at Lombardi Comprehensive Cancer Center, said that one of the biggest debates in the field of breast cancer is whether to treat very small tumors.
Since they had such small tumors and presumably a better prognosis, these women weren't included in [the pivotal clinical] trials of trastuzumab. But these new data show that without trastuzumab therapy, these patients clearly have a worse prognosis, she said.
Dr. Liu noted said that some clinicians are already offering trastuzumab to patients with smaller tumors. The new data may make more physicians think about using it, she said.
Charles L. Vogel, MD, Senior Research Advisor in Breast Cancer at Aptium Oncology in Boca Raton, FL, said, These two studies are tremendously important. Whenever you go to a meeting, everyone always asks what to do with very small tumors.
Before we had no answers, but now we have a few nice pieces of data to support trastuzumab therapy, he said.
Dr. Vogel added that while he believes many physicians treat Stage TIb tumors, they draw a line in the sand at 5 mm.
The M. D. Anderson study, which showed no significant difference in recurrence rates between women with Stage TIa and TIb HER2-positive tumors, suggests that even the smallest tumors may benefit from trastuzumab, Dr. Rakkhit said.
Dr. Gonzalez-Angulo said that one open question is whether these patients will benefit from trastuzumab alone or whether they need trastuzumab plus chemotherapy.Article Outline | Back to Top Ongoing Trial
A Phase II clinical trial, led by Eric P. Winer, MD, may offer some clues. The trial is looking at the effect of postoperative trastuzumab and paclitaxel on breast cancer recurrence in women with node-negative, Stage TI tumors that are HER2-positive.
The trial is still open, said Dr. Winer, Director of the Breast Oncology Center in the Department of Adult Oncology at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School. Patients, who are being enrolled at the time they are starting their adjuvant therapy, receive paclitaxel and trastuzumab every week for 12 weeks, followed by trastuzumab every three weeks or weekly, for 40 weeks.
The study is designed to test a regimen with relatively limited toxicity in a group of patients who are at low risk of disease recurrence, but are still thought to be at sufficiently high risk of recurrence to warrant trastuzumab-based therapy, Dr. Winer said. It's estimated that the study will be completed in 2010.
Jan 23, 2012 06:05PM Hindsfeet wrote:
I'm glad Beesie said not all stage 1 or treatments are the same. This has been a hot topic for me as some of you know. I feel for women dx with stage 1a. It is very, very, very confusing. You take for granted that staging is for treatment purposes...at least that is what you are told. I am stage 1a with NO node involvement and the recommended treatment is herceptin, chemo, taxomifin or Als and scans ... plus a mx. For another who is 1a it might be a lumpectomy with rads and tamoxifen only. It's all over the boards...literally :)