Update on triple negative breast cancer
One of the challenges of triple negative breast cancer is that it is defined by what it is not (ie ER/PR-, HER2-), rather than what it is. This broad subgroup of breast cancer is therefore more heterogeneous in nature than many people actually realise. It also means that unless we uncover the various driving mutations underlying it, we are sadly doomed to the world of repeatedly poor response rates. We can do better than this.
The other day I saw a new paper in the Journal of Clinical Investigation (open access) that caught my eye:
“Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies”
Researchers from Vanderbilt-Ingram cancer centre identified six different subtypes relating to this disease. Six!
They found the subtypes by looking at gene expression profiles in 21 different breast cancer sets and identified the triple negative cases (n=587). From these cases, cluster analysis identified the six TNBC subtypes. These subtypes included:
- two basal-like (BL1 and BL2)
- an immunomodulatory (IM)
- a mesenchymal (M)
- a mesenchymal stem–like (MSL)
- a luminal androgen receptor (LAR)
Here’s where it gets very interesting though – these newly identified subtypes are sensitive to different therapies:
“BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin.
M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor).
The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling.”
In other words, based on identifying a women with triple negative breast cancer’s precise subtype, they could be used as a potential biomarker for selection into appropriate clinical trials. By doing this we may be able to screen those women more likely to respond to a given therapy and then determine in randomised controlled clinical trials whether the molecular hypothesis is indeed correct before treatment in a broader population.
Many of you will no doubt be wondering how this relates to PARP inhibitors such as iniparib, which until recently were the hottest thing in breast cancer. The simple answer is, it doesn’t. None of the subtypes identified appear to have a known sensitivity to PARP inhibitors, that I know of. What is important is that new molecular subtypes have been identified and these appear to be sensitive to therapies either already available commercially or in clinical development for other tumour types.
Overall, this is an excellent and well designed study with the most useful and instructive findings. It’s like finding 6 needles in a haystack at once and will hopefully guide us in a much more focused way. I really do hope that clinical researchers respond quickly and get some new clinical trials going up and running soon with appropriate patient selection criteria in triple negative breast cancer.
We need more cowbell like this in cancer research. This is the stuff dreams are made of.
References:
Lehmann, B., Bauer, J., Chen, X., Sanders, M., Chakravarthy, A., Shyr, Y., & Pietenpol, J. (2011). Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies Journal of Clinical Investigation, 121 (7), 2750-2767 DOI: 10.1172/JCI45014
14 Responses to “Update on triple negative breast cancer”
Thanks for this helpful summary of the new findings, Sally. I hope that by 2020 doctors will be prescribing drugs based on the BC sub-subtypes.
Hi Elaine,
Thanks for stopping by…. I think it will happen much sooner than that if the subtypes identified are sensitive to already approved drugs. In the case of tumours where we have little success, it only takes a couple of peer reviewed papers based on positive phase I or II data to often lead to Compendia listing, prescribing and reimbursement. I’m hopeful.
I hope they move quickly with this . I want to live!
I was just diagnost at 45 yrs old with Triple Negative Breast Cancer. It is about 3 inches in my left breast and they are wanting to do a second look ultrasound because the MRI showed some possibly in my right breast also. The surgeon is still wanting to do just a lumpectomy and i am really scared because everything that I have read on this type of cancer I feel that I should have a mastectomy to make sure there is no reacurrance. I don’t understand why she gave me options and then when I told her what I wanted she said no. Why give the options then? I am researching everything I can. My surgeon hasent told me what else will happen except that I will be sent to an Oncologist after. Can anyone give me an idea of what I am looking at for treatment?
I would totally get a second opinion! Our docs are supposed to present us with our options and let us make the decision. They can make recommendations but ultimately the decisions are ours to make. Sounds like you need more information overall before you can make an informed decision. Before you have surgery you can meet with your oncologist. He/she may give you the choice to do chemo before surgery (this is what I did and a lot of women are doing) but it depends on the individual. Go to http://www.breastcancer.org an excellent source given to me by OHSU knight cancer institute where I’m being treated. Where do you live?
I hope this helps. Please don’t be afraid to ask a ton of questions and buy a voice recorder for all of your doctor visits. Also take someone you trust with you.
Hope
So very sorry to hear about your diagnosis – totally agree with Amie and would seek a second opinion and counsel. I would start with several things:
1) Stop, breathe deeply and think about embarking on some research before rushing into a decision
2) A great source might be to ask for help from other breast cancer patients and physicians such as Cancer GRACE which has a helpful breast cancer forum see here: http://cancergrace.org/forums/
3) Another good patient forum source is Gilles Friedman’s ACOR: http://acor.org
4) Sign up to Twitter and join in the breast cancer twitter chat #bcsm that involves patients, physicians, surgeons and advocates see here: https://twitter.com/search/%23bcsm
If you feel able, let us know where you are and we can make some suggestions for a second opinion to help with your decision making.
The day before I turned 60 I was diagnosed with TNBC. Large aggressive tumor in my left breast. I took 3 rounds of chemo, 3 different types every 3 weeks for 9 weeks. Then I had a bilateral mastectomy and another 3 rounds of chemo the same as before chemo. The first 3 doses shrunk the tumor from a 6 cm to a 2 cm size. After the 2nd round of chemo I had 3 small tumors in my lung and l in my spine. I am very anxious for a effective treatment to be released. I was scheduled to have radiation but because of the new tumors I had to delay that. Seawee 34 I wish you good luck. I hope this infor gives you some idea of what you might expect.
Sally,
Thanks so much for writing about this. I heard good information — and excitement – from researchers from the Baylor College of Medicine at a conference last week in Houston. Hoping, hoping, hoping.
Jody
In response to Seawee34 – I hope you find the following information helpful:
While “triple negative” breast cancer does tend to be more aggressive, and our treatment options are more limited (for example, we cannot use anti-estrogen medications like tamoxifen or aromatase inhibitors and have to rely more on chemotherapy), please remember that every patient, every tumor is different. Take your time to get an additional opinion or two and to really understand all of your options.
For most women with breast cancer, there is the choice between breast conservation (lumpectomy followed by radiation treatment) or mastectomy. We used to use size of the tumor as a criteria but now we more rely on the tumor size relative to the breast size – can the surgeon remove the tumor with a rim of normal tissue (the margin) and leave an acceptable cosmetic result?
For large tumors, especially triple-negative, we will often use chemotherapy before surgery to reduce the size of the tumor, and possibly reduce the amount of normal tissue removed at the time of surgery – this allows more women to be candidates for breast conservation and studies have demonstrated no decreased survival from this approach. In addition, realize that even after mastectomy, there is a small possibility that the cancer may return – a mastectomy is not a guarantee against recurrence.
A recent study published in the Annals of Surgical Oncology looked at women who were treated for triple negative breast cancer and found no difference in local recurrence (the cancer coming back in the breast), and their conclusion is that triple negative breast cancer is not a contraindication to breast conservation : http://www.springerlink.com/content/36740mq458h19608/
I hope you find this information helpful and at least a little encouraging. The references listed by the others above are all excellent, and the best advice I can give you during this difficult time is to breathe, and take your time gathering your information and opinions – don’t rush to any decision.
In response to Seawee34 – I hope you find the following information helpful:
While “triple negative” breast cancer does tend to be more aggressive, and our treatment options are more limited (for example, we cannot use anti-estrogen medications like tamoxifen or aromatase inhibitors and have to rely more on chemotherapy), please remember that every patient, every tumor is different. Take your time to get an additional opinion or two and to really understand all of your options.
For most women with breast cancer, there is the choice between breast conservation (lumpectomy followed by radiation treatment) or mastectomy. We used to use size of the tumor as a criteria but now we more rely on the tumor size relative to the breast size – can the surgeon remove the tumor with a rim of normal tissue (the margin) and leave an acceptable cosmetic result?
For large tumors, especially triple-negative, we will often use chemotherapy before surgery to reduce the size of the tumor, and possibly reduce the amount of normal tissue removed at the time of surgery – this allows more women to be candidates for breast conservation and studies have demonstrated no decreased survival from this approach. In addition, realize that even after mastectomy, there is a small possibility that the cancer may return – a mastectomy is not a guarantee against recurrence.
A recent study published in the Annals of Surgical Oncology looked at women who were treated for triple negative breast cancer and found no difference in local recurrence (the cancer coming back in the breast), and their conclusion is that triple negative breast cancer is not a contraindication to breast conservation : http://www.springerlink.com/content/36740mq458h19608/
I hope you find this information helpful and at least a little encouraging. The references listed by the others above are all excellent, and the best advice I can give you during this difficult time is to breathe, and take your time gathering your information and opinions – don’t rush to any decision.
I just found out that I am triple neg and I am at a loss as to where i should get more information. I live in dc md area. I want the correct chemo etc and I just don’t know who is up on this
I am so sorry to hear this news. The good news is that you have an excellent breast cancer physician called Dr Robert Miller at Johns Hopkins in your area who I would recommend you check out. His contact details are here:
http://www.hopkinsmedicine.org/doctors/results/directory/profile/0024370/robert-miller
thank you for answering. Do you also know of a center in US that uses the penquin cold caps in the rapunsel project for keeping hair during chemo? thanks meg
Sadly I don’t, Meg, but I do know some people who might. If you are on Twitter, there is a breast cancer chat on Monday evenings at 9pm amongst patients, physicians and caregivers using the hashtag #bcsm. I will ask one of them to pop by and ask for you.
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