Recurrence and hormone therapy

By | Wed November 22, 2017

Even since Cancer Research UK posted an article reporting on a research report by Pan et al (2017), I have seen a lot of discussion on the topic of hormone positive breast cancer prognosis and hormone therapy.

The article itself caused a lot of concern surrounding two key things: (1) the continued risk of recurrence through 20 years, and (2) anti-hormone therapy treatments. I want to talk about the second issue first.

The inclusion criteria for the Pan et al (2017) research (that is, the women who were counted in the study) were those who were “scheduled to receive endocrine therapy for 5 years then stop, regardless of actual adherence” (p.1837). What this means is that the research study itself can in no way make any comment about the efficacy of endocrine therapy (also known as anti-hormone therapy such as tamoxifen or aromatase inhibitors).

Confusion around anti-hormone therapy stemmed from this quote in the Cancer Research UK article:

Gray said that the study shows it’s important for women with ER+ breast cancer to continue with their anti-oestrogen therapy for longer than the recommended five years. He hopes that these results will motivate women who are experiencing side-effects while on this treatment to persevere with it.

The problem is, that the research report by Pan et al (2017) does not speak to the efficacy of hormone therapies. In the discussion section (this is where the researchers look at the literature and their research and interpret what it might mean), it says:

Although reliable trials evidence is not yet available on the long-term effects of extending endocrine therapy for 5 additional years on mortality, an absolute reduction of a few percentage points in the risk of distant metastases over the next 15 years might well be possible even for such low-risk women, with correspondingly greater absolute benefits for women with larger tumors or node-positive diseases (p. 1844)

The area of specific interest to me in the above statement is that there is no evidence yet on the long-term effects of extending endocrine therapy. It does no good to cure cancer if the cure itself kills you from heart disease or makes your bones crumble from osteoporosis. Endocrine therapy is not without risks, and often involves horrible quality of life issues.

I want to talk more about what the Pan et al (2017) says. The research applies to easily stage survivors who were diagnosed under the age of 75 who has either stage 1 or stage 2 cancer with less then 10 lymph nodes involved. In addition, to be included in the study, patients had to be disease free after 5 years. The study looked at recurrence rates at the 5-20 year interval.

Note also that in order to get 20 year data, it means that some of those who were included in the study were treated 20 years ago. Chemotherapy regimes and practices have changed, as have surgery techniques, since the time of diagnosis. The study anticipates that those who are diagnosed today will have statistically better outcomes than those represented in the study.

In reading the article I was put at ease a little by seeing this image.

screen-shot-2017-11-13-at-2-59-01-pm

Although the risk of recurrence doesn’t stop over the 5-15 year period, it helped me to understand that my 20-year absolute risk isn’t my year-over-year risk. What I mean by that is, looking at the bottom yellow line, that if my 20-year risk is 15 percent, that doesn’t mean that each year my risk is 15 percent, rather at 5 years my risk is 3%, at 10 years it is 8%, etc. That actually made me feel better. For some reason, I had in my head that if I’m at a 30% risk, that I am always at a 30% risk – such that for any given day, I had a 30% chance of learning that my cancer had come back. That isn’t right thinking at all. The picture helped me realize how the statistics actually worked. It helped me feel less worried about where I am today. (note this is just one picture, there are a bunch of others in the report).

It is still a bit of a blow to think that regardless of how long I live, I will have a risk of recurrence. I knew it, but it didn’t really sink in until I saw the graphs. What this also made me think is that because of my young age at diagnosis, the longer I live, the more likely the cancer will come back (assuming the slope of the graph follows as it has the first 20 years).

There were some specific predictors mentioned in the report that I thought were of interest:

Although all the women had been clinically disease-free for many years, the original tumor diameter and especially the original nodal status remained powerful determinants of late distant recurrence, even during the second decade after diagnosis. Within each TN-status category, distant recurrences continued to occur steadily throughout the person from 5 to 20 years. (p.1840)

This is encouraging for me because my nodes where negative.

Tumor grade and the presences of Ki-67 antibody…were important independent factors of prognostic value during the first 5 years but were of only moderate relevance thereafter. (p.1841)

This is also interesting, as it says that the grade of the tumor (how fast it was growing) is a predictor for the first 5 years but less important after 5 years (still relevant, but only moderately so).

And finally:

The prognosis for women in particular TN categories has somewhat improved owning to earlier diagnosis, more accurate tumor staging, and better surgical, radiation, and systemic therapies.

In conclusion, even after 5 years of adjuvant endocrine therapy, women with ER-positive , early stage breast cancer still had a persistent risk of recurrence and death from breast cancer for at least 20 years aft er the original diagnosis. (p.1845)

Reference

Pan, H., Gray, R., Braybrooke, J., Davies, C., Taylor, C., McGale, P., . . . EBCTCG. (2017). 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med, 377(19), 1836-1846. doi:10.1056/NEJMoa1701830

If you want to read the full article and are unable to access it, leave me a message and I’ll email it to you.

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