Episode 23 Shownotes - Understanding Triple Negative Breast Cancer

You are listening to Best Life After Cancer, Episode 23.

Hi, My Best Lifers and welcome back! I am launching my first weight loss coaching group November first. There is a focus for breast cancer patients, but it is awesome for anyone who has struggled with weight, and just not known why they can’t follow their plan. It is not a medical treatment – I don’t prescribe pills or surgery, I help you figure out what in your brain is keeping you from doing the things you know you need to do to be healthy. I’d love to have you join us. You can get information on my website, Best Life After Cancer under the services section.

In addition to working on that, I am coaching myself into loving fall (it used to be my least favorite season). And it is working! I have been so grateful to see all the beauty around me this fall. I am planning an upcoming podcast about this topic, so stay tuned. This week is the 3rd podcast in breast cancer month, and is by request a medical one about triple negative breast cancer. I am going to go through what it is, why it is worse, what the standard treatment is, and also dispel some myths along the way! As always, I am a doctor, but not your doctor, so run all medical decision making by your primary team.
So let’s dive in. First, what is triple negative breast cancer, also known as TNBC. Breast cancers run the spectrum from less aggressive to more aggressive. This is in part determined by the presence or absence of markers on the surface of the cancer cells that can be targeted by our therapies. Normal breast cells have estrogen and progesterone receptors, that respond to the hormonal signals of our bodies, telling them to multiply during preganancy to get ready to feed an infant, or cut back after menopause when we no longer need them. When a cancer cell starts to grow, often it still has these receptors, and is using the estrogen and progesterone in our body to stimulate their growth. There are pills, including tamoxifen, used for premenopausal women, and aromatase inhibitors, used for postmenopausal women. The simplified action of these pills is that they cut off the food supply to the tumor cells, effectively starving them. The next in terms of aggression is ER/PR and Her2 positive cancers. Her 2 is another molecule that we have targeted treatments for, including Herceptin. In triple positive patients, they will receive hormonal therapy and Herceptin. Then, ER/PR neg, Her 2 pos. They will often get chemotherapy and Herceptin. Finally are the triple negative cancers. What makes these so aggressive is that they are not listening to your body’s signals at all. They are growing all on their own, making what they need to grow, and not affected by the targeted molecules we have. This means that chemo will still be helpful, but hormonal therapy or Herceptin, the meds used after chemo, are ineffective.

First, let me tell you – staging for breast cancer currently is super complex. It includes the T or tumor stage, meaning size and invasion into skin, chest wall and more. N stage is nodal staging. There is both a clinical nodal staging, used before the nodes are removed, based on what we see on imaging and feel on exam, and a pathologic N staging, which is what we see under the microscope after surgery. M is presence or absence of known metastatic disease. The staging also includes the Grade (goes from 1-3, and is how the tumor cells look under the microscope), ER/PR status, Her2 Status, and oncotype, more or less than 11, if that is used (not used in triple negative cancers or Her2 pos cancers). The staging is in the show notes, describing in detail how stage is determined. Anatomic Staging means pre surgery, pathologic staging means using post surgery.

My charts wouldn't past, so here is a link to a site with staging for breast cancer:

https://emedicine.medscape.com/article/2007112-overview?src=ppc_google_rlsa-traf_mscp_emed-hdle-cohort_md_us 

So – let’s talk about who needs chemo with a TNBC. The treatment paradigm for TNBC is a bit different than for other breast cancers, and uses chemotherapy more frequently and earlier in the treatment path. The NCCN puts out guidelines that are considered the standard of care in the US. The NCCN guidelines for tumors less than or equal to 5 mm, node negative is for NO chemotherapy. In a 5mm cancer with a node met that is 2mm or less, chemo should be considered. Tumors 6mm to 1cm, node negative, chemo can be considered. For tumors over a cm, chemo should be given, unless there are extenuating circumstances, like advanced age or other severe medical issues that preclude chemo. Any nodal disease over 2mm also warrants chemotherapy, with the same caveats. Here is a good place to dispel a myth about TNBC. I have seen posts on Facebook that this type of cancer is not truly curable. This is incorrect. There are many long term survivors of TNBC, and these include people with LABC involving the nodes. The cure rate does go down in those without a pCR, but still we see cures, especially in those who’s nodes were negative at the start.

In terms of what chemotherapy, randomized trials have shown that the addition of a taxane to AC improves outcome over AC alone. The use of a platinum agent is controversial. Some studies showed an improved pCR rate. Long term outcomes are not yet known. This is not considered standard, but can be considered in selected patients. There are trials ongoing for patients who do not achieve a pathologic CR, and I will discuss this more at the end of the podcast.

One of the big areas of discussion in TNBC is chemo before surgery or after. There is not a clearly defined point at which chemo before surgery is thought better than chemo after surgery in this group, but a few things are clear. Randomized trials of chemotherapy have shown similar long term outcomes whether it is given up front or after surgery. Second, a pathologic complete response, meaning no tumor left in the breast or nodes at surgery after chemotherapy, is associated with a better disease free survival and overall survival, especially in TNBC. Finally, care should be taken after preop chemo to make sure that appropriate local therapy is employed, because inadequate local therapy is associated with an increased risk of failure. This means imaging should be used to determine what needs to be removed, and radiation employed in patients having a lumpectomy. If a mastectomy is planned, imaging may not be necessary.

There are some clear benefits to chemotherapy up front. Up front chemo is also known as neoadjuvant chemo (abbreviated as NAC). It can be used to make inoperable tumors operable (ie. Big fixed lymph nodes, breast mass attached to the underlying muscles). It can also possibly make breast conservation possible in masses too big for that at the start. It can provide prognostic information about the responsiveness of the tumor to chemotherapy. It allows us to see if a regimen isn’t working (meaning tumor isn’t shrinking or is actually growing) to stop an ineffective treatment to switch to a more effective one, sparing a patient chemotherapy that will not help cure their disease. It may let us know who needs MORE treatment after surgery (for instance, patients who do not have a path CR). In many patients, chemo up front also allows for time for genetic testing and surgical planning, if considering a mastectomy with reconstruction. It may allow for lesser surgery or radiation, if all nodal disease is eradicated with chemotherapy (note, this is 100% on a case by case basis, and NO clear group can be given the go ahead for less surgery or less radiation as a group).

The cautions with NAC – it is possible to overtreat if clinical stage is overestimated (ie, nodes look like involved, but are not biopsy proven and end up just being inflammatory or the body’s response to the tumor). There is also the possibility of progression during treatment if the tumor is not responding to treatment.

Clear candidates for NAC include bulky or matted nodes (meaning they are fixed together in a clump), N3 disease, and T4 tumors. In patients with operable breast cancer, NCCN states that preop chemo is preferred in TNBC patients with T2 or greater disease or nodal disease. Another consideration is in pts with a large primary/small breast who want breast conservation. Those who are NOT good candidates for NAC are those with extensive in situ disease, as the risk of overtreating is high (think 2 cm of DCIS with 1 mm of invasive disease – mass may feel or look large, but DCIS does NOT need chemo under any circumstances). This is one of the places where it really isn’t one size fits all, and treatment of stage 1 TNBC is variable based on doctor and patient preference, differences in practice patterns in different parts of the country and more. Just remember, that for stage 1 cancer, the cure rate is equivalent with NAC or post op chemo, and we don’t have to have the prognostic info of response for you to be cured.

What workup is appropriate before NAC? If the tumor is T2 or larger, or node positive, the recommended workup includes a history and physical exam, mammograms with US if needed, some form of axillary assessment (usually with US) and biopsy of suspicious nodes, pathologic review, confirmation of ER/PR and HER2 status, genetic counseling (note that currently TNBC is an indication on it’s own qualifying for genetic testing), and fertility counseling if premenopausal. A pregnancy test is needed in all premenopausal women prior to chemotherapy. Studies that can be considered, but are not mandatory include labwork with CBC, liver function tests and alkaline phosphatase, that can be abnormal if there is bone involvement, CT of the chest and abdomen, or abdominal MRI, bone scan or PET scan, and breast MRI. More extensive testing is often performed in locally advanced TNBC, to make sure there is not metastatic disease already present. In stage I cancer, additional testing is usually NOT performed, as the vast majority of findings will be red herrings, meaning not cancer, and will delay the start of treatment unnecessarily.

What is recommended after treatment? In the absence of symptoms, no distant screening studies are indicated. This is explained further in Podcast 21 on testing after cancer treatment. Mammos and physical exam are a must, becauase if there is a recurrence in the breast or nodes this is still curable. MRI is used in many patients with a difficult exam or strong family history, among other reasons. It is recommended that women make all effort to maximize their survival with what they can control, which includes an active lifestyle, with a goal of 150 minutes of mild to moderate activity per week, limiting alcohol (I tell patients 5 drinks per week or less), and maintaining an optimal BMI (20-25). There are multiple free BMI calculators online to figure out yours.

Finally, no discussion of TNBC would be complete without a discussion of clinical trials. There is a website, clinicaltrials.gov (link in the shownotes) where you can search by breast cancer, and add triple negative as a qualifier. https://clinicaltrials.gov/ct2/results?cond=breast+cancer&term=triple+negative&cntry=US&state=&city=&dist=
There are currently 508 trials in the US for women with TNBC, with 209 actively recruiting. Some are looking at additional therapy in pts who do not achieve a complete response. Some are looking at monoclonal antibodies in conjunction with vaccines. Trials change monthly, so an in depth discussion is not really useful here. Let’s just say, if you are young, with a TNBC, with a poor response to NAC, an evaluation at a tertiary care center to discuss available trials is certainly not unreasonable.

Finally, let’s dispel a few myths. This type of breast cancer is CURABLE. It is not a death sentence. It IS being aggressively researched to continue to find drugs to help after standard chemotherapy. It is less common, but not something unknown, or so rare that we don’t know how to deal with this. Like any other cancer, part of this journey is dealing with what’s in your body, and an equally important part is dealing with what’s in your mind. Living in fear of your diagnosis is problematic for many reasons. It increases stress hormones that can suppress immunity. It also destroys quality time. I love the quote, Worry doesn’t decrease tomorrow’s risk, it destroys today’s peace. For certain, if you are spending your time worrying, you are losing that time, and there is no worry bank where you can get it back. If you have a year before your cancer comes back, I am sure you want to enjoy every minute, and not spend it worrying. If your cancer is never destined to come back, then you could waste the next 10 or 15 years worrying. In no case does the worry give you more time, reduce your risk, or help you enjoy the time you are given. My favorite book quote is from Gandalf to Frodo in the Lord of the Rings trilogy. (I KNOW – SO GEEKY). Gandalf says “All we have to decide is what to do with the time that is given us”. Fear can be addressed, and if it is a challenge, I hope you will consider working with me to address it. The first step to getting help with the fear is to join the survivor’s group on my FB page, Best Life After Cancer, MD! To my friends on the Triple Negative Breast Cancer facebook group – this one was for you! I hope this was helpful. I’ll talk to you soon!