San Antonio Breast Cancer Symposium 2015. Dec.8-12

JohnSmith

Biomarker news - HER2 (ERBB2) mutations in mBC:

[P3-07-05] "Non-amplification ERBB2 genomic alterations in 5,605 cases of refractory and metastatic breast cancer: An emerging opportunity for anti-HER2 targeted therapies"

The enrichment of ERBB2mut in CDH1 mut mBR was significant (p=0.0006) and associated with relapsed Lobular mBC.
(According to Dr. Hal Burstein of Dana Farber, the FoundationOne test revealed HER2 mutations in 2.4% of breast cancers, with 33% being Lobular.)

Conclusions: In this large series of 5,605 mBC, 20% of the total ERBB2 alterations were non-amplification ERBB2mut not detectable by standard of care IHC and FISH slide-based HER2 tests. Given the demonstration of ERBB2mut driven mBC responsive to anti-HER2 targeted therapies in this study, expansion of clinical trials designed to detect these ERBB2mut cases with CGP and optimize the targeted therapies for these patients is strongly recommended.

JohnSmith

ILC / Lobular news:

[S1-02] Lymphocytic infiltration in invasive lobular breast cancer

Background: The presence and prognostic value of tumor infiltrating lymphocytes (TILs) in invasive breast carcinoma has been demonstrated in several studies, especially in the triple-negative and HER2-positive subtypes. So far, TILs have not been investigated with sufficient detail in invasive lobular breast cancer (ILC).
Here we therefore aimed at:
First, assessing the distribution of stromal TILs in ILBC;
Second, correlating the presence of TILs with standard clinical and pathological markers;
Third, exploring associations of TILs with recurrent genomic alterations; and,
Fourth, comparing the lymphocytic composition of ER-positive/HER2-negative lobular to ER-positive/HER2-negative ductal tumors.

Conclusion: In this work, which reports to our knowledge on the largest series of ILC ever assessed for TILs, we showed that most ILCs were characterized by low lymphocytic infiltration. Besides the association of TILs with clinical and pathological features of ILBC patients, we found that higher TIL levels were observed in the presence of specific mutations and copy number alterations. Higher numbers of TILs were associated with worse prognosis at the univariate analysis. Finally, based on the assessed markers, we have no evidence of differential lymphocytic composition between ER-positive/HER2-negative lobular and ductal tumors.

Moderators

Hey all -- also see our new thread:

SABCS 2015: Breaking News at San Antonio Breast Cancer Symposium

JohnSmith

HER2+ Biomarker news:

S5-01. Whole exome sequencing of pre-treatment biopsies from the neoALTTO trial to identify DNA aberrations associated with response to HER2-targeted therapies
Conclusions: There are no high frequency recurrent single mutations associated with response to HER2-targeted therapies, other than PIK3CA. We identified several biological pathways, including RhoA activity, and a network of PIK3CA associated genes that are significantly associated with response when affected by mutations, however, different genes are mutated in different individuals.

Media article: "Study probes genes for clues to drug resistance in aggressive breast cancer"
excerpt: By sifting through the 20,000 protein-encoding genes in the human genome, Yale researchers discovered new complexities behind drug resistance and identified patterns of mutations that could predict which therapies will benefit patients with aggressive breast cancer.
Using tissue from the international NeoALTTO study, the Yale team sequenced 203 HER2+ samples to assess which mutations in which genes predicted response or resistance to HER2-targeted therapies. In the study, patients with early stage breast cancer were treated pre-operatively with either paclitaxel chemo in combination with one of two breast cancer drugs (Trastuzumab [Herceptin] or Lapatinib [Tykerb/Tyverb], a protein kinase inhibitor), or with the drugs alone.
"The key finding is that different cancers acquire resistance to Trastuzumab through different mutations in different genes. The silver lining is that these genes participate in biological processes that are all connected through the PIK3CA gene", says Dr. Lajos Pusztai of Yale."
* Note: The downside is that PIK3CA drug trial results have been mixed.

voraciousreader

http://www.eurekalert.org/pub_releases/2015-12/msk...

How hopeful should we be with liquid biopsies.....

voraciousreader

http://www.medscape.com/viewarticle/855765

Narrow margins are OK!

Anonymous

Hi Team, just saw that the Luminal A cancers do not benefit from chemo. Isn't that exactly what the Oncotype tests state? How many women have endured chemo without benefit? How many more as we wait for the validation of Oncotype?

MinusTwo

Thank you VR and John. So nice to have these quickly at hand. Even if I don't understand all of what I'm reading, I'm forming questions for my MO.

MusicLover

I second what MinusTwo has said thank you.

CatsRus

me too...thank you

Fallleaves

Thanks for the highlights Voraciousreader and JohnSmith! (Lots to digest....)

voraciousreader

http://mobile.philly.com/health/?wss=/philly/health&id=361563751

🤗

voraciousreader

http://www.medscape.com/viewarticle/855862

voraciousreader

Skip Chemo in Young Women With Common Breast Cancer Subtype?

Kate Johnson

December 09, 2015

SAN ANTONIO, Texas — Premenopausal women with Luminal A breast cancer, a common, intrinsic subtype, can consider skipping chemotherapy altogether and still expect a good prognosis, even when they are node positive, according to a new analysis of an old Danish study.

"This is clearly part of a body of evidence [in breast cancer] that's building up…that we can probably back off on the aggressiveness of our treatments and still achieve the same results," said investigator Torsten Nielsen, MD, PhD, from the University of British Columbia, Vancouver, British Columbia, Canada.

The new findings from the Danish Breast Cancer Cooperative Group 77B DBCG77B) study, which Dr Nielsen presented here at the San Antonio Breast Cancer Symposium (SABCS), raised some eyebrows given that chemotherapy is considered standard in premenopausal breast cancer.

But the question is a relevant one, noted Virginia Kaklamani, MD, of the University of Texas Health Science Center San Antonio and a codirector of the meeting.

As an investigator on the ongoing prospective SWOG RxPONDER trial (S1007) which is investigating a similar question, Dr Kaklamani said that the DBCG77B results "confirm what we thought — that we kind of don't need chemotherapy for these patients."

She also said the results expand her own sense of what is possible.

"This is another step and for me it gives me a little more confidence in my premenopausal women not to push chemotherapy. In our practice we would consider at least for a 55 or 60-year-old woman not giving chemotherapy if she had no hormone positive disease, but in premenopausal women we tend to not think about it," Dr Kaklamani said.

The new analysis used a prospective-retrospective design — in that it used tissue samples taken 25 years ago when the DBCG77B trial randomized patients to chemotherapy or no chemotherapy — a process that would not be considered ethical today (Cancer. 2010 May 1;116(9):2081-9).

At that time, 1146 premenopausal women with high-risk disease (tumors > 5 cm or positive axillary lymph nodes regardless of hormone receptor or HER2 status) were randomized to one of two active treatments — single-agent oral cyclophosphamide (C), or classic combination cyclophosphamide, methotrexate, and 5-fluorouracil (CMF); or 1 of 2 nonchemotherapy arms — levamisole, or placebo.

"They did not receive endocrine therapy, but they did however get what would be considered adequate local therapy by today's standards — a mastectomy supported by axillary node dissection and chest wall radiation," he said.

Ten-year disease-free survival (DFS) was better in the chemotherapy arms (55.5% in the C arm, 48.8% in the CMF arm) than the nonchemotherapy arms (38.6% in the control arm and 35.2% in the levamisole arm).

Immunohistochemical staining of the remaining available DBCG77B tissue samples revealed that chemotherapy improved DFS in 468 non-Luminal A patients (hazard ratio [HR] 0.50), but it had no benefit in 165 Luminal A patients (HR 1.07, P < .05).

Molecular testing is the key to differentiating between breast cancer subtypes, and Luminal A subtype can be determined by adding Ki67 to the regular biomarker panel run on every breast cancer, Dr Nielsen told Medscape Medical News, adding that this test is frequently available at local pathology labs.....

http://www.medscape.com/viewarticle/855703

To read the rest of the article, the link might not work. Just Google the title of the article and it might pop up. Furthermore, if that doesn't work, register at medscape!

voraciousreader

i just want to comment on the article that I just linked. Please make a note that the title is somewhat misleading due to caveats in the study. Since many of the patients who received chemo didn't receive the newer generation of chemo, some physicians were still hesitant of the findings. That said, with newer pathological testing, going forward some day SOON, we will have a better understanding of which premenopausal patients can rest easier if they DON'T do chemo.

voraciousreader

i also want to add one more comment....Due to earlier studies such as SOFT and TEXT, younger premenopausal patients are being given the choice of ovarian suppression. So the question being raised is....will there ever be a study that can truly nail down which premenopausal women can safely avoid chemo if the landscape of treatments rapidly changes? I think the next round of TAilLORX and the RxPONDER results might be the game changers....

voraciousreader

http://www.medpagetoday.com/MeetingCoverage/SABCS/...

Above link to study is also worth reading. Also worth noting is the point that Luminal A tumors signal a good pprognosis, AND because they are usually slow grow8ng, it makes sense to avoid chemo because chemo works best on rapidly growing cells.

123JustMe

Thanks VR!

coraleliz

So, the older generation of chemo isn't beneficial? Also known as chemo-light or CMF? I've seen many here at BCO go that route, early stagers with slow growing tumors. If nothing else, doctors really need to reconsider & maybe stop offering this to patients.

voraciousreader

cora....I don't think that is where they are heading until they can safely conclude that the data meets the highest level of evidence. That's what the NCCN and the other major groups guidelines are for. It is all about building on the evidence and creating a Standard of Care.....

coraleliz

I guess where I'm coming from is what I was told 4+years ago by my MO. And that the newer generation C&T is believed to be better. And some of us(including myself) that more chemo would be better with the slower growing tumors(6 cycles instead of 4).

Anyway I thought this was interesting regarding MX vs LX

Lumpectomy's Edge: All Clinical Smoke and Mirrors?

Better survival due to patient selection, not mastectomy inferiority

http://www.medpagetoday.com/MeetingCoverage/SABCS/...

voraciousreader

cora....I think the landscape has begun to change in the last 4, 5 or even 6 years with respect to not recommending chemo for slow growing cancers. I think with the oncotypeDX test now NCCN recommended since 2011, physicians are growing stronger in defending the lack of benefit of chemo for those patients. But again, the evidence still hasn't reached that critical level.

With respect to lumpectomy and radiation vs. Mastectomy....since the first published data a few years back on this subject, I've been following this data as well. I find it interesting....that is all I will say. That said, this subject really presses lots of people's buttons as well! Oy! If only it was THAT simple.....

doxie

I don't know if there are set criteria yet for Luminal B, yet. Last I checked it was a moving target. But generally 10 % or less for PR+ and/or 20% or more for Ki67.

Different researchers have chosen different thresholds for a variety of reasons. I'm solidly Luminal B so I've not kept track of the boundary between A and B. As with cancer all edges are fuzzy.

voraciousreader

Rose .....there are no simpleton questions! Everyone's questions deserve answers. That said, taking the time to read these studies and then formulate questions is admirable. I just wish the answers were more straight forward. I like what Doxie said....sometimes the lines are "fuzzy."

voraciousreader

😇

cp418

I've browsed several research articles on this topic but did not save them. Some of the data was gathered from older studies to test tumor pathology and evaluate those patients who did vs did not receive chemo - plus Tamox may not have been used and AI were not available. From what I recall, the Ki67 cut off => 14 indicates Luminal B and it is more common to have positive node(s). PR can be positive or negative if I recall but higher PR might be good. Luminal B because more aggressive should respond better to chemo. Interesting was the majority of the pathology reports were for Luminal B in that data evaluation. In the past, patients with positive nodes (not micromets) were always recommended to have chemo which seems to support this BC status. Now it has become more complex with the Oncotype testing which may better determine Luminal A vs B subtype.

I fall into Luminal B subtype Ki67 = 20 and 1 positive sentinel node. I don't regret receiving chemo and pray I never have to go through it again.

edited to add this link:

http://www.breastcancer.org/research-news/20121217...

http://www.breastcancer.org/research-news/some-tre...

Fallleaves

Regarding the Smoke and Mirrors article, I don't agree with this statement: "The conclusions are more a result of selection than a result of the operation," said Kevin Hughes, MD, of Massachusetts General Hospital Cancer Center in Boston. "The patients with small, well-differentiated tumors got lumpectomy, and those with poorly differentiated, larger, and node-positive tumors got mastectomy. Of course, the mastectomy group is going to do worse."

The authors of the study controlled for confounding factors (age) and did sub-group analyses (looking at just T1N0 patients, etc) and their findings held up. So it wasn't just a matter of comparing apples to more advanced oranges.

muska

i just read the abstract in the link that coraleliz posted. I don't think the abstract lists the confounding factors that were applied. Age is only one of many. I suppose number of positive nodes, multifocal or not, grade, size, some molecular characteristics, etc. should be taken into account as well. I have no idea how confounding factors were applied. The devil is in the details. Without having that information I can only say that I have no reason not to trust the opinion of Dr. Kevin Hughes who unlike me most likely read the entire study and unlike me understands statistical research as it applies to breast cancer.

Fallleaves

Muska, here are some of the other confounding factors the article mentioned (I did not mean to indicate age was the only one): "Patients who had breast-conserving therapy were younger. As compared with the mastectomy group, the lumpectomy patients had tumors that tended to be smaller, well differentiated, unifocal, ductal and localized to inner or outer areas of the breast." And the article also said Dr. Siesling corrected for those potential confounding factors and still came up with a 19% lower survival hazard for lumpectomy vs. mastectomy. It just seems weird that Dr. Hughes is acting like she didn't take those things into consideration, when she clearly did.

muska

It would be very interesting to see how Dr. Siesling corrected her calculations for the several factors you listed above, but the abstract that I read does not have these details. Dr. Hughes probably looked at those details before making the comment he did.

I am not sure applying confounding factors is the way for such generalized conclusions.

Disclosure: I am not a patient of Dr. Hughes.