The SOFT Study and how sometimes reading study results is emotionally hard

We are getting buried in snow here. Buried. 90+ inches since January 23rd. Public transportation often cancelled. Its been physically and psychologically taxing. We are inventing new words to describe the side effects of the snow: Snager, Snochosis, Snaddness. However, it has also left me with an additional feeling: gratitude. I am so thankful that the winter of 2013 was not like this. Having to go to radiation daily while wondering if your bus is going to show up? I feel for those who are in the midst of treatment right now. And I'm thankful to be where I am. Here are a couple of photos of my backyard this morning:

 

When waking up to the midst of a blizzard I did what everyone else does. I made a batch of whole grain blueberry muffins and read the latest breast cancer study from the New England Journal of Medicine. (Citation: Francis PA, Regan MM, Fleming GF, et al. Adjuvent Ovarian Suppression in Premenopausal Breast Cancer. N Engl J Med 2015;372:436-446). This is known as the SOFT trial; Suppression of Ovarian Function Trial. 

The basics

The SOFT trial randomized 3066 premenopausal women to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression or exemestane (an Aromatse inhibitor, decreases the circulating estrogen level) and ovarian suppression.  This study also did something that most studies have not done, they stratified their results based on subjects having needed chemotherapy vs not. This is a very important detail because most often those who have had chemotherapy are survivors who had more aggressive cancers, cancers that had already spread to the lymph nodes.  The study followed the 3,066 women for 5 years and the primary end point they were looking at was disease free survival. 

These are my notes. "* You bet your ass it is". Very scientific. And yes my pen is pink

The Results

When the investigators did the large group analysis overall it was found that adding ovarian suppression to tamoxifen did not provide a significant benefit. Bummer, right? Well, the study found something that is worth further investigation. And its very important for what this study deemed the very young sub group. This is for women that were younger than 35 years. 233 such women were included in the primary analysis. And this is where the interesting part occurs. In this subgroup (my people!) the "rate of freedom from breast cancer at 5 years was 67.7%" on tamoxifen alone, 78.9% for those on tamoxifen plus ovarian suppression and 83.4% for those on exemestane plus ovarian suppression. Whoa. This clearly is underpowered, but does designated that further investigation into the true effects of ovarian suppression and its  benefit should be studied in the "very young" sub group. The study authors write 

With a median of 67 months of follow up the number of breast cancer recurrences observed was large enough to indicate that including ovarian suppression as a component of adjuvant therapy can meaningfully reduce recurrences in this cohort. 

I know that one study does not make treatment plans, but this is exciting stuff. However, it may be a little premature in follow up as perhaps 5 years is too short a time. This study was pretty rigorous in design and removed the previous confounder that is present in many other breast cancer studies and that is the treatment with or without chemotherapy.  Also, an important part of this study was the definition of all the patients as being premenopausal. The study defined premenopausal based on estradiol blood levels (estrogen in the blood) and not on the presence or absence of menses.

The Results based on the non-science portion of my brain 
What! 1/3rd of those who are 35 years old or younger had a recurrence while on tamoxifen. That seems a bit high, right? That means about 15 women enrolled in the study had recurrence during the 5 year period. But, it says recurrence not death. So that is not great, but ok.

Also, not great to read was the overall survival of those who had had prior chemotherapy was lower than those who had not had prior chemotherapy (and was found to be statistically significant). I mean it makes sense because those offered chemotherapy usually have more aggressive disease. However, it is still hard to read. Especially, because again the very young subgroup 94% all had had chemotherapy.

Overall, like most studies more investigation is needed. But, very interesting implications for young survivors. For further recap of this study you can watch the video below produced by the Young Survival Coalition