What does it mean when tumors change receptor status in retesting?

Forty-one percent of breast cancer tumors changed receptor status following neoadjuvant chemotherapy (before surgery) in a recent study presented at the 2013 Breast Cancer Symposium in San Francisco (Abstract 48).  For example, this means that an estrogen-receptor-negative tumor might have changed to an estrogen-receptor-positive tumor, or vice versa.  Specifically:

• 20 percent changed from hormone receptor positive to HER2-positive or triple-negative

•12.5 percent changed from HER2-positive to triple-negative;

• 2 percent changed from triple-negative to HER2-positive.

A change in receptor status change was associated with improved recurrence-free survival but had no impact on overall survival.

At a median follow-up of 40 months, 5-year overall survival was 73 percent for patients with a change in receptor status and 63 percent for those with no change; 5-year recurrence-free survival was 63 percent and 48 percent. 

To clarify: patients whose tumor changed receptor status had fewer recurrences, but they did not live longer overall. So, basically, for those of us who are interested in living through cancer—as in, all of us—the results are pretty much a washout.   Remember, though, overall survival means those who are still alive at the end of the study, with deaths related to any cause, not just cancer.  

What is most significant to me, though, is the whole issue of tumor status change in the first place.  Did the tumors actually change, or were the tests  inaccurate to begin with? Or was the second test flawed? Lajos Pusztai, MD, PhD, of Yale Cancer Center told Ob. Gyn. News that the problem could just be technical problems with the testing.  And, he says, when tumors are retested, they change receptor status 20 percent of the time, whether they have been treated or not.

So if your doc mails your tumor sample to a different lab, you have a 20 percent chance that its receptor status will be different in retesting.  That is, if you originally tested estrogen-receptor-negative, and had those results sent to a different cancer center, your tumor could end up testing as estrogen-receptor-positive in the new analysis.

But, Pusztai says, you should still have the same therapy, even if your receptor status varies:

“It would be dangerous to actually withhold endocrine therapy or anti-HER2 therapy when tumors turn negative on a second assay. You don’t know which assay may be wrong. Be very careful in making decisions based on conflicting results.”

To this I say, WHAT, WHAT, WHAT?????  TNBC tumors get some heavy chemo—does he say we should go through with that even if we might not actually have TNBC?  Is this why some TNBC tumors respond to tamoxifen—because they weren’t actually TNBC?

I say, challenge any inconsistency.  If you can afford it, get retested and, if there is a discrepancy, ask for a third test.   Cancer treatment is no picnic and you want to be sure your treatment is geared correctly to your cancer.

• Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

• Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Ionizing radiation in puberty linked to ER-negative breast cancer later in life.

Exposing young women and girls under the age of 20 to ionizing radiation can substantially raise the risk of their developing estrogen-negative breast cancer later in life, according to research published in the journal Stem Cells August 2013.

“Our results are in agreement with epidemiology studies showing that radiation-induced human breast cancers are more likely to be ER negative than are spontaneous breast cancers,” says Sylvain Costes, a biophysicist with the Lawrence Berkeley National Laboratory.

Epidemiological studies have shown that girls under 20 given radiotherapy treatment for disorders such as Hodgkin’s lymphoma run about the same risk of developing breast cancer in their 40s as women who were born with a BRCA gene mutation. Costes and colleagues concluded that self-renewal of stem cells was the most likely responsible mechanism.

The researchers are now looking for biomarkers that would identify young girls who are at the greatest breast cancer risk from radiation therapy. The results of their study show that the links between ionizing radiation and breast cancer extend beyond DNA damage and mutations.

“Essentially, exposure of the breast to ionizing radiation generates an overall biochemical signal that tells the system something bad happened,” Costes says. “If exposure takes place during puberty, this signal triggers a regenerative response leading to a larger pool of stem cells, thereby increasing the chance of developing ER-negative breast cancers later in life.”

—from a news release from Lawrence Berkeley National Laboratory.

• Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

• Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Does tamoxifen have a place in TNBC treatment? The answer is still "no."

Women with the BRCA 1 or 2 mutations may benefit from the use of tamoxifen, even if they are estrogen negative, but the evidence so far is not convincing.  According to research in the Journal of Clinical Oncology, use of tamoxifen reduced the risk of cancer in the opposite breast by more than half among both BRCA1 and BRCA2 mutation carriers no matter what the receptor status was of the original tumor.

The study looked at information on 1,583 BRCA1 and 881 BRCA2 mutation carriers who took tamoxifen after their breast cancer diagnosis;  of these 24 percent of the BRCA 1 took tamoxifen and 52 percent on the BRCA 2 carriers took tamoxifen.   

This is an intriguing study and I would not make much of it until or unless a clinical study is started to look at the issue more closely in a more controlled environment. The numbers of women on tamoxifen were small in the research, because tamoxifen has not been recommended for TNBC and many cases of cancer among those with the BRCA mutations are TNBC. Also, we're not sure how other variables were controlled, or if they were, so those could play a part. So I would not start thinking tamoxifen is a benefit to TNBC—there's way too many questions right now, and the side effects of tamoxifen are significant. The general recommendation is not to use tamoxifen for TNBC, and that recommendation still stands.

• Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

• Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Cure Magazine Focuses on TNBC

Cure magazine recently ran a comprehensive article on TNBC.  It was well-researched and balanced.  I love the introductory survivor story, plus the many quotes from docs who emphasize that the disease is survivable.  The writers used the statistic that 30 percent of TNBC cases are fatal.  That does mean that 70 percent aren't.  Still, to clarify, stage matters, and early stage TNBC is highly survivable, with some studies showing more than a 90 percent survivor rate.

And, after five years, survivor rates for TNBC are better than for non-TNBC.  So, yay there!

I was in the article's sidebar, which focused on the fact that the disease is far less ominous than some think.  My mantra:  Most women survive TNBC and go on to live long, meaningful lives.  I am seven years past diagnosis, and I know many women who are several decades past.  So take that, TNBC.  My favorite quote in the entire piece is in this sidebar, from Lisa Carey, M.D., of the University of North Carolina, who has an impressive record of TNBC research:

“People go online and Google TNBC, and they see all these scary stories. But a half-inch, node-negative TNBC tumor is not high risk, no matter what.” 

• Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

• Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Sloppy Reporting Affects Too Much Cancer Writing

Reporters:  Precision is essential in health writing  

Patients: Read carefully and learn to spot misinformation and dangerous generalizations

I have been a journalist for 46 years, 30 of that teaching at some level. My son is a journalist, as are most of my close friends. Yet one of my biggest frustrations since my cancer diagnosis is with my own profession. 

Most journalists have more of a job than they can handle right now, so I offer a few rules for them about breast cancer reporting, skewed toward information about triple-negative breast cancer (TNBC), which gets especially distorted in the media. What tripped my trigger today was a story in KGW.com, a station in Portland Oregon, but it has been an issue with The New York Times, medical journals, blogs, and just about every form of medical or health information.

1. No one type of breast cancer is THE most aggressive.  Not TNBC, not Her-2 positive, not inflammatory, all of which are repeatedly given that description in outlets large and small. 

Which is THE most aggressive?  Plenty of all types.  Even early-stage hormone-positive breast cancer can be aggressive with the wrong mix of genetics (the BRCA genetic mutation and others that researchers are still uncovering), family history, and numerous environmental, health, and lifestyle issues (insulin resistance, weight, alcohol abuse, and so on).

Some forms of TNBC are more lethal than some forms of hormone-positive, and less lethal than other forms.  And so it is with all types and subtypes.

2.  There are successful treatments for most forms of TNBC.  Yet journalists easily say things such as, in the KGW.com piece, “Women with triple negative breast cancer don't usually respond to most traditional therapies.”  I honestly appreciate that qualifier, “usually.”  Neverthless, the statement is inaccurate.  It is true that TNBC tumors are not responsive to estrogen-altering drugs such as tamoxifen and Arimidex because the disease is not fueled by estrogen.

But TNBC responds well to typical chemotherapy—better than other forms of cancer respond, in fact.  So women with TNBC usually get their drugs in the form of chemo, either before or right after surgery, rather than in five-year doses, as is the case with patients with estrogen-positive disease.

Treatment for metastatic TNBC—stage IV—remains difficult, and many of those patients do not respond to current therapies.  But fewer than 10 percent of patients with TNBC have stage IV, which means that 90 percent may respond well to treatment.

So the helpful qualifier in that statement would be “Metastatic TNBC does not usually respond well to most traditional therapies.”

3. Readers internalize your words.  Last week I talked to a woman who had been given an excellent prognosis form her doctor, yet still thought her outlook was grim because she read a news release saying TNBC was lethal.  Communications research demonstrates this phenomenon—we’re more likely to consider media reality as the real deal instead of our own lives.  Everybody lives in cool apartments and houses on TV, so you believe that to be true in real life, despite the fact that most of your friends have standard-issue digs with furnishings from WalMart.  Same way with health issues.  Ominous news in the media feels more accurate that your doc’s more measured approach.

4. The generalizations you use can loop around to negatively affect your readers’ and listeners’ health.  I recently met a highly educated woman with a medical background who thought that it did not matter that her TNBC was stage 1.   “Stage doesn't matter with this disease, does it?” she asked.  She was ready to give up.  Of course stage matters.  Stage 1 TNBC is much less aggressive than stage 4 of anything else.  The great majority of women with stage 1 TNBC survive—as many as 90 percent in some studies.

Still, because she thought TNBC was automatically aggressive, she was giving up, and few battles in health or otherwise are won by giving up.

So do your research and don't lump early stage with late stage disease. The research reported on by KGW.com was on the drug PLX2297, which may be effective against TNBC.  I cannot find the research the reporter alludes to, but I did find a clinical trial for PLX3397 in connection with Eribulin for metastatic TNBC.  Metastatic is late stage. Metastatic is a much different disease from non-metastatic. Know the difference and include it in your story.  It actually only takes a word.

5. Remember your vocabulary.  Lethal means deadly. So if you tell me my disease is lethal, you are telling me it will kill me.  Yet most women with breast cancer, including TNBC, live happy lives long after diagnosis.  I have talked to a great many of them.  They compete in triathlons, have babies, tend their grandchildren, get remarried, buy cottages by the ocean.

6.  Get your stats straight or don't use them.  Just as all breast cancers are different, so are their prognoses.  Saying that TNBC patients have “another five to eight years to live,” as KGW.com reported, is outrageous.  There is no research to back this up.  Most recurrences of TNBC come in the first three years, but a host of studies show that the majority of women with the disease make that marker easily and live disease-free for decades. In fact, the prognosis for women who make it past that three-year mark is better than for women with hormone-positive cancer.   I have interviewed countless women who are 20 years past this diagnosis.  Sadly, I have lost friends before the three-year mark.  There is no one prognosis, but the reality is that most women survive beyond "five to eight" years.  Don't tell readers they’ll likely be dead in five years.  Really, I have to say that?

7.  Never settle for a one-source story.  This is pretty basic and is true of all journalism, but especially for health.  That source could be wrong, inarticulate, promoting an agenda, or speaking in medical shorthand that his colleagues might comprehend but which may confuse or frighten their patients.  Researchers naturally want to show the importance of their findings and, in so doing, could mischaracterize the seriousness of a disease. This information is too important to let one individual set the tone.  At least link to organizations with a broader perspective.  Numerous sites exist for accurate breast cancer information, including breastcancer.org, the Triple-Negative Breast Cancer Foundation, Living Beyond Breast Cancer, and of course, this blog.

• Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

• Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Carboplatin shows better response for TNBC patients, but what about toxicity?

There has been a good amount of evidence that cisplatin and carboplatin are effective for TNBC patients, especially those with BRCA mutations.  A recent German study used a pretty potent cocktail to specifically test the the effect of carboplatin on pathologically complete response, which is tied to a better prognosis for TNBC patients.   And it did work a bit better: 

Those treated with carboplatin had a somewhat higher pathologically complete response—43.1 percent of those with carboplatin versus 36.9 percent of those without.

For my money, that is not much of an advantage when you look at this heady chemical mix: carboplatin added to paclitaxel plus Adriamycin, plus Avastin—in weekly doses. 

Note that:

•  Avastin is no longer approved for  breast cancer in the U.S., so this treatment is not an option here

• 40 percent of the patients on this protocol  had at least one serious adverse effect.   
Diarrhea was the most common.

• The typical chemo treatment for TNBC in the U.S. is in two-week intervals.  Weekly chemo seems especially harsh, giving the body little time to recuperate. 

Read the full story on ASCO Post.