BRCA1 Gene Mutation Associated With Neoadjuvant Chemotherapy

Nearly half of breast cancer patients carrying the BRCA1 gene mutation experience a complete pathological response (pCR) the disappearance of all evidence of disease from the breast tissue and lymph nodes regardless of disease stage after standard neoadjuvent chemotherapy, according to new research from The University of Texas MD Anderson Cancer Center.

The study, published online in The Journal of Clinical Oncology on September 6, is the largest study to date to find that the pCR rate is significantly higher in BRCA1 carriers (46 percent) than in women carrying the BRCA2 mutation (13 percent) and non-carriers (22 percent). Among all the women, researchers did not find a statistical difference in overall survival rates, but noted that BRCA1 carriers who achieved a pCR had better five-year, relapse-free survival and overall survival rates.

BRCA1 and BRCA2 belong to a class of human genes known as tumor suppressors. The mutation is inherited and increases a woman's chance of developing breast cancer with more aggressive features by 80 percent. Researchers aimed to determine whether women with and without the mutations would respond differently to the same treatment.

"While hereditary breast cancers typically carry aggressive tumor features compared to sporadic breast cancers, we found that BRCA1-related tumors were as responsive and sensitive to anthracycline and taxane-based chemotherapy as were sporadic breast cancers," said Banu Arun, M.D., professor in the Department of Breast Medical Oncology at MD Anderson and lead author of the study. "These findings may help physicians determine the best treatment method for this subset of women with unique genetic mutations."

For the study, researchers used MD Anderson's Breast Cancer Management System Database to identify 317 women at varying disease stages who received neoadjuvent chemotherapy and clinical genetic testing for BRCA1 and BRCA2 between 1997 and 2009. Fifty- seven women were BRCA1 carriers, 23 were BRCA2 mutation carriers and 237 were non-carriers. After chemotherapy, 61 patients received breast-conserving surgery, while 256 opted for mastectomy.

Median follow up time for the patients was 3.2 years, at which point 22 percent of patients experienced disease recurrence or death. There were no significant differences noted in survival outcomes with respect to BRCA status and type of neoadjuvent chemotherapy received.

According to Arun, there is no consensus on the most effective chemotherapy regimen for treating women who carry the BRCA mutation, due to a lack of prospective studies.

"This new insight tempts us to speculate that the presence of the BRCA1 mutation determines how some women will respond to neoadjuvent chemotherapy. However, we need future prospective studies with larger cohorts and longer-term follow up to validate these findings and determine optimum treatment," Arun noted.

Source: University of Texas M. D. Anderson Cancer Center
http://www.medicalnewstoday.com/releases/233965.php

Mindy,

Please vent away!  I completely understand your frustration when we're facing these types of decisions and delays.  Will they be doing any type of scans (ultrasound, mammo, MRI) during treatment to see if the tumor is shrinking or will they just wait until surgery to know if you have pCR?

Donna

Hi Mindy,

Mindy, 

Hi again Mindy,

The mouthwash they prescribed for my wife is called "Cool's solution". I don't know much about it but the pharmacist had to mix it up - it was very inexpensive. I'm sure you can google it and find out what is in it. Hope this helps!

Wade

Hi Wade and Mindy,

Wade, I was diagnosed 4/29 and also finished my neoadjuvant chemo 9/23! Sounds like we had the same things at the same time!

Mindy, I understand all of your concerns completely. My tumor was growing very fast. When two weeks passed between when I found the lump and the first onc appt, I felt like it had grown. My onc made the comment 'not even the fastest growing cancers grow that fast' but then said nothing when the MRI confirmed that it had. It had grown 1.6 cm in the 9 days from mammo to MRI and was another 9 before I started chemo...very scary. It was 3.9 cm on the MRI. They did not biopsy my nodes prior to chemo.

My onc is a late 50's, 60ish guy, very by the book, only recommneds what published research supports. He was recommneding surgery first. The surgeon that I had seen, is 30's new to the area, and his research love is TNBC. He pushed for neoadjuvant chemo and has told me more than once that treatment for TNBC is headed towards all neoadjuvant chemo but we don't have all the research to support that yet and many docs will only do what is proven by research.

Interestingly enough, even though MDA has the research to support the Taxol first, I had the AC first, every other week for 4 cycles, then 12 weekly Taxol. Somehow, I missed the post indicating the Taxol first, so I was really freaking out when I saw the study indicating Taxol first and the improved outcomes but I was already doing the opposite. Very much like Wade's wife, two weeks into the treatment I had to show the onc the tumor and by three weeks- weeks, not treatments, I could no longer feel it myself! I assured myself that even though that wasn't what MDA would do, it was clearly working for me. Who knows, maybe it wouldn't have been as great for me the other way. Anyway, two weeks ago I had my follow up MRI, followed by mammo, magnified views, and ultrasound and the tumor is GONE! They can not find it at all, only the titanium marker!! I am having a lumpectomy on the 25th and hoping they find pCR!! (BRCA neg)

As far as side effects, the AC was much harder for me overall. They suggested that I do the anti-nausea meds for the first three days, which I did, but I never noticed a difference when I stopped them, just felt crummy all the time. I had some mouth sores, but nothing bad, almost always gone in 2 days. With Taxol, I seemed to do fine other than fatigue. I had tx on Friday and about #9, I started feeling crummy on Sundays. About #11, the terrible muscle aches set in and are just starting to lessen (yesterday the doc suggested I try magnesium). The Monday after #12, I woke up with my fingernails hurting horribly and was sure they would fall off. 3 weeks later, within the last week, they hurt less and looks like maybe they will stick around. Last week I had a lot of swelling that a few days of Lasix fixed. I have some mild neuopathy that didn't start showing up until #11 and I am hoping progresses no further, but no guarantees. So really, the bulk of my side effects from Taxol were at the very end or after it! And while I would rather not have them, it is a small price to pay. I am within target weight, reasonable fitness level, so don't know how much this helped. I also took supplements to help. Unlike many oncs, mine did not object.

I understand wanting it gone. I would also point out though, that chemo is a systemic drug, so it can be working on anything else there since our TN nemesis does not need to spread through the lymph nodes. Doing chemo first does enable them to monitor your response, but if you did adjuvant chemo, you wouldn't know if it was affecting any of the little buggers that might be floating around, so to speak. Since you are BRCA+, I assume that they are still recommneding the mastectomy. A colleague had TNBC 3 years ago but never did testing since her kids were adopted, despite a strong family hx. A few months ago, she ended up with a second type of BC and tested BRCA positive and now has had the dbl matectomy. If you are at MDA, I assume they are being very mindful of the genetic piece!

It must be very hard feeling like you are going against your initial instinct. There is a ton of research out there, and great success stories with neoadjuvant!! I hope all of this was not tmi. I truly hope that you soon start feeling the tumor shrinking,feel better about the decision, and kicking some cancer butt! Best of luck to you!

Deb

Dear Mindy,
It sounds as through you are having one of those days that I referred to as:
"Holding my breath" in anticipation that the chemo is really working. That causes hyperventilation and then I really go to pot. The difference was, I had the surgery first and never had the assurance that the chemo was working.

Please BREATHE and I'm praying that your tumor will just melt away. It is unsettling in the beginning, no matter which route you take.

God Bless,
Lillie

Here's to shrinking tumor!!!!!

Thanks so much Donna, Blair, Deb, Wade, Lillie and Tina for sharing with your responses.  You gave some very important and interesting points to think about, good tips and kind thoughts. With your input and after my local Onc visit today,  this is starting to take a positive twist.

I had my 2nd Taxol treatment at her office after we got caught up.  She's a "surgery first"  kinda doc,  though certainly does her share of neoadjuvant treatment when a tumors are larger than 5 cm or are in a difficult position.  Her preferred treatment is A/C  followed by Taxol.  We're obviously carrying out MDA's t sequencing (for now) since I committed and treatment is underway.  She's totally supportive- we'll monitor by ultrasound here and she highly recommends their check-up/monitoring expertise at several intervals like we agreed at MDA unless a change is noticed by me and a change of course is necessary.  Ego never gets in the way of her extensive breast cancer (including triple negative) expertise.  She has more breast cancer patients than any other oncologist in Oklahoma.

By simple physical examination the tumor has grown since the first treatment. What I find really odd along with the growth is the way it's actually morphed into a different shape & dimension (which I only noticed the day before).  What was a vertical mass is now horizontal in shape.   She said the total mass volume has probably decreased.  Plus, a centimeter tape isn't the ideal way to measure...though it gave us a fair indication until my ultrasound next week.   Maybe I should be, though I'm not overly concerned after her explanation I wish I could articulate, but can't at the moment.  I'll find out and post if anyone is interested.

Having nothing to do with the published report of sequencing, my Onc believes the Taxol first methodology sequencing has its own merit. She obviously prefers A/C first or she wouldn't use it.  For those of you who received A/C first, I wouldn't worry too much for all the reasons already mentioned.  I know I'd love to see my tumor shrinking.  I wasn't jumping with joy over growth, albeit hopefully very temporary or I'll be a relentless squeaky wheel.

Any other neo & Taxol first people out there with growth before shrinkage?  I met a lady at MDA whose tumor on Taxol shrunk down to nada after her 3rd treatment = 3rd week.

One more question.  My regular GYN wrote an RX for Clonazepam for anxiety with 1 refill when I was first diagnosed.  I don't take it often as it just makes me sleepy.  I noticed many of you, mention use of Ativan, like your wife Wade.  My Onc wants me to change nausea med coupled with Ativan instead.  Realizing everyone responds differently, does Ativan make you overly sleepy?  I ask because my anxiety peaks when I first wake up in the morning- and starts to diminish when I get up and get busy- but I'm sleepy in the process.  I've tried it at night and it doesn't prevent the morning freak-out.  You should see how quickly I hop out of bed lately.  Those attacks are the pits.  I thought they were a thing of the past as I hadn't an episode for about 3 decades.




Edited by mindy555 - Oct 18 2011 at 11:53am

Hi Mindy,

I saw your post and wanted to respond while things were fresh in my memory. My wife's tumor grew substantially between diagnosis and treatment, we think(by we, I mean the docs-this is not my bailiwick) primarily due to swelling from the needle biopsy. It then seemed to shrink pretty quickly after starting the A/C. Kerri (my wife) was getting biweekly treatments, with a Neulasta shot in between.

I can't comment on the Ativan, as my wife only took it to help her sleep, which may or may not tell you anything.

As an aside, I'm a hunt and peck typist, so if my answers seem terse, it's probably because of my typing limitations...

 

Good morning, ladies

Wish us luck. We're off today for lumpectomy, sentinel node biopsy and Medi Port removal. Here's hoping we popped ol' Green Teeth right between the eyes...

Wade