My Story

My breast cancer case was called “medically interesting” because there is no universal standard of adjuvant care for the type and size of my tumor. I asked 10 oncologists what to do after surgery, and I got several different answers.

The cancer was HER2-positive, and the tumor was classified as “very small” or “tiny” at 1.5 millimeters. There was no evidence the cancer spread beyond my breast.

For any patient with a tumor over 1 centimeter, chemotherapy and trastuzumab (Herceptin) as adjuvant treatment is a clear-cut standard of care for HER2 positive breast cancer.

But for a subcentimeter HER2-positive tumor, the guidelines from the National Comprehensive Cancer Network (NCCN) say to “consider” those drugs – it is not automatic.

The graphic below shows the how my tumor stacked up within the guidelines. The graphic is sized for a computer screen, but is to scale on all devices.

NCCN HER2-positive guidelines

There are no current medical trials that focus on T1a tumors. One reason is because they are rare. Usually, tumors are larger when first discovered, although that trend is slowly changing thanks to earlier detection.

Each of the ten opinions I had from oncologists for adjuvant treatment could be justified as being the “right one” based on the limited information available about T1a tumors.

But size was not the only factor doctors considered on the question of my adjuvant treatment. They also looked at tumor features and biomarkers, or the biology of my tumor — every patient is different.

Biomarkers and tumor features

Triple positive

My “very small” tumor was also what’s called “triple positive.” This simply means it tested positive for two hormones – estrogen and progesterone – in addition to being positive for HER2.

Those hormones encouraged cancer growth. The good news is that endocrine drugs like tamoxifen can suppress hormones to slow or prevent future cancer growth.

But the big thing speeding up my cancer growth was the HER2. So what the heck is HER2, anyway? In the most basic terms, HER2 is a gene that mutates. It starts to make extra copies of a protein by the same name – HER2.

This special protein encourages growth even more than hormones. This is what makes this cancer subtype so aggressive. The good news is trastuzumab can suppress HER2 and slow or prevent growth.

HER2/CEP17 ratio

This is the rate at which HER2-positive cancer cells make protein for division and growth. This ratio is usually identified on something called a FISH test that sometimes can supplement a basic pathology report. Anything equal to or greater than 2.0 is positive for HER2. The higher the ratio, the faster the cancer grows.

Basically, if initial testing shows a tumor might be HER2-positive, additional testing will be done, usually a Fluorescence In Situ Hybridization test, called FISH. Doctors look at two numbers in test results to determine if a tumor is HER2-positive, a signal ratio and copy number.

A signal ratio above 2.0 should be treated as HER2-positive, according to relatively new guidelines by the American Society of Clinical Oncology (ASCO). The former threshold was 2.2.

What does any of this mean about the cancer coming back? No one really knows for sure, especially not me. One study found no correlation at all between the HER2/CEP17 score and recurrence rate. But doctors still like to know what the ratio is.

I guess I just felt better knowing mine was 2.6, and not as high as some cases I’ve read about – like 6.0.

Tumor grade

Tumor grade can be an indicator of recurrence. Higher grades are more aggressive.

Grade 1 cancer cells look slightly abnormal. They tend to spread more slowly than grade 2. Grade 2 cells look more abnormal and spread at an intermediate rate. Grade 3 cancer cells look highly abnormal compared to healthy cells, and these cells spread the fastest.

My tumor was grade 2. If it had been grade 3, would my treatment decision have been different? Maybe. Maybe not.

Ki-67 index

Uncontrolled growth is the hallmark of cancer. The Ki-67 index helps estimate growth. In the most basic terms, this index is the proliferation rate, or the growth rate.

Ki-67 is a protein cancer cells make when they are getting ready to divide and grow. The Ki-67 percentage indicates what proportion of the cancer cells are dividing and growing. A higher percentage means more cells are growing.

There is not a universal standard to measure Ki-67. Some doctors call under 10 percent low, 10 to 20 percent intermediate, and over 20 percent high. Others say anything below 14 percent is low, and over 14 percent is high. Still others use 15 percent as the dividing line.

The Ki-67 level was 12 percent in my tumor. Generally, larger tumors and higher grades will have a higher Ki-67 percentage.

Cancer subtype

Some retrospective studies have examined whether a cancer subtype increases risk for recurrence. Mine was classified as luminal B, which grows faster than luminal A. Luminal B usually has high Ki-67 levels, but not always — mine did not. Luminal B cancers are HER2-positive, and so by the nature of the HER2-positive status, these cancers are more aggressive.

More tests??

Every single study and every single doctor will state the need for more tests and more research to better know how to treat women with “very small” tumors like mine. They will look to the biomarkers and tumor features when size doesn’t provide an easy answer.

Tests like Oncotype DX are common. It measures how effective chemotherapy may be on a particular cancer, and other tests can measure a cancer’s risk of recurrence, to a degree. It’s important to note, tests like MammaPrint are not for HER2-positive cancers. (Some ASCO guidelines are here.) The MammaStrat test can be used with HER2-positive, but it’s usually given with respect to chemotherapy – and much larger tumors.

I did not have these tests. The majority of doctors did not recommend it based on all of my other pathology information. Just know that these tests are out there, and you can easily find more information on them.

Adjuvant recommendations for me

So, now with all of the above in mind, here are recommendations I received for my “medically interesting” cancer case.

Oncologist opinions.jpg

I had 10 opinions. (An 11th opinion came in after I made my decision, and so it’s not counted here.)

Three American oncologists are counted twice because they recommended I “consider” chemotherapy and trastuzumab, followed by five to ten years of tamoxifen. These three doctors also recommended I have the Onctotype or Mammostrat tests, but everyone else said those were not relevant for me – including two other American doctors.

By the way — just how effective is trastuzumab without chemotherapy? Studies show it does lower the recurrence risk in early stage HER2-positive breast cancer, but by how much is inconclusive. Trastuzumab can cause heart damage.

Dr. Edward Romond helped run trials for use of trastuzumab on early breast cancer patients. I found an interview he did with the American Society of Clinical Oncology about small and “very small” HER2-positive tumors. Here is his take:

“The guidelines indicate that for node-negative, T1a and T1b tumors, chemotherapy plus trastuzumab can be considered. But we discuss with our patients who clearly have T1a cancers whether a risk for distant recurrence approaching 1% is worth a year of treatment.”

Five doctors recommended trastuzumab and tamoxifen.

Five doctors recommended only tamoxifen – for up to ten years because I’m pre-menopausal. (Two of these five actually recommended I strongly “consider” tamoxifen– one said at least try it. They believed my recurrence risk seemed to be extremely low based on my biomarkers and tumor features, no evidence of lymph or vascular invasion, and I had a bilateral mastectomy that has left me with 3-5% of breast tissue.)

I reviewed all opinions. I talked with my husband. I talked with my parents. I researched as much as I could about my situation. I prayed. I listened to my intuition. In the end, I decided to try tamoxifen — nothing else.

Kotor cliff me
This is me, about six weeks post mastectomy in Kotor, Montenegro. I’m an early retired world traveler with my husband, and my surgery was performed in Croatia.

If I have any lingering doubts, it’s about the large mass of DCIS that prompted the bilateral mastectomy in the first place. Did pathologists miss any other very small tumor? Was there micro invasion on a blood vessel they missed? Could a different lymph node have been positive? Should I have had another pathology test on my breast tissue? I also wonder about a surgical lumpectomy the year before my bilateral mastectomy. That surgery was done at a primitive facility in Mexico without any image guidance. Did that doctor ‘stir things up’?

These questions will eat me alive if I let them. Nothing in life is guaranteed, especially for a woman who’s been diagnosed with invasive breast cancer. We forever live with a whispered fear: will the cancer come back?

I made the best decision I could with the information I had, and that’s all I can do. What happens next is up to God or the Universe or a Higher Power or whatever you want to call it. I only know the answer to that recurrence question is not up to me.

I’m an early retired budget traveler with my husband. I had my bilateral mastectomy in Zagreb, Croatia, by a fantastic surgeon who came highly recommended by his peers. I had my 3D mammogram and stereotactic biopsy in Split, Croatia, by other wonderful medical professionals. You can read more on my diagnosis abroad here; about my double mastectomy in a foreign country here; about my decision to live “flat” with no reconstruction here. Other information such as how I found a surgeon in a foreign country, my post-cancer checkups abroad, and why DCIS can be dangerous, can be found here.



The information contained in this blog is not intended to be used for medical diagnosis or treatment. It should not be used in place of the advice of your doctor or other qualified health care provider.