Pillar 2 - Breast Cancer, page-55

The interconnected relationship between breast cancer, obesity, and heart failure, and where bisantrene fits in. I want to highlight this point as I believe it is fundamental to understanding the importance and need of a drug like bisantrene.

Key points:

- Risk of breast cancer diagnosis increases with age - average age 63 years

- Median age by region has increased since 1950's and is expected to continue

- Postmenopausal obese women at increased risk of breast cancer

- Obesity prevalence is increasing

- Current breast cancer population at serious risk of heart failure

- Current anthracyclines have a therapeutic dose limit due to massive increase in heart failure risk

- An alternative option is available with historic data that supports its efficacious and, most importantly, safe use

The risk of a breast cancer diagnosis increases with age, with the average age of diagnosis falling around 63 years of age. This average age has increased from 57 years, indicating that those who are diagnosed with breast cancer are getting older and older (1). The global population aged 60 years or over numbered 962 million in 2017, more than twice as large as in 1980 when there were 382 million older persons worldwide. The number of older persons is expected to double again by 2050, when it is projected to reach nearly 2.1 billion. This is supported by the median age by region increasing in all from 1950 to 2020, and is expected to continue rising (2).

Figure 1: Breast cancer cases per year compared to age at diagnosis

Figure 2: Change in median age by region.

Also, among postmenopausal women (roughly say >55 years), those who are obese have a 20-40% (and even 50%) increased risk of developing breast cancer when compared to normal-weight women (3). The worldwide prevalence of obesity nearly tripled between 1975 and 2016. If current trends continue, it is estimated that 2.7 billion adults will be overweight, over 1 billion affected by obesity, and 177 million adults severely affected by obesity by 2025 (4).

The convergence of both of these points indicates to me that the world is getting older and more obese, both of which are fundamental risk factors for obesity. Also, people aged 65 years and over are at the greatest risk of heart failure (in fact, it’s a leading cause of death among women) (5), also postmenopausal obese women (over ~60) have 50% increased risk of heart failure than non-obese women (6).

Clearly, we have the convergence of multiple risk factors. For those patients who are obese, postmenopausal, and above the age of say 60 (all factors of which are expected to increase over the coming years) that get breast cancer (also increasing - maybe a correlation there?), what are the treatment options available to them?

Current chemotherapeutic standard of care for breast cancer involves the use of anthracyclines, which are damaging for the heart. Anthracyclines have a lifetime maximum dose (550 mg/m2, but doctors typically will not go above 250 mg/m2) that cannot be exceeded without causing lifelong irreversible damage to the heart (7). This limits the opportunities to treat breast cancer effectively.

Figure 3: Long-term increase of heart failure risk with anthracycline dose

What this means is the use of anthracyclines for breast cancer is increasing the risk of heart failure in a population that likely already has increased risk of heart failure, which, in my opinion, highlights the clinical significance of bisantrene. Calling on data discussed in the Rediscovery of Bisantrene paper (Figure 4).

Figure 4: Bisantrene safety profile

I would like you to pay special attention to the last sentence highlighted above and compare them to the maximal dose of other anthracyclines; 7080 mg/m2 of bisantrene with minimal cardiotoxicity compared to 550 mg/m2 of doxorubicin and likely lifelong increased risk of heart failure. I cannot overstate the role that bisantrene can play in the coming years. Bisantrene represents a class of drug that can provide efficacious chemotherapeutic care, whilst also being safe for the heart in a population of people that are older and heavier and that are at increased risk of heart failure before touching anthracycline based therapies.

You make the decision about what you believe makes sense.

All IMO - DYOR

1. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/incidence-invasive

2.https://www.visualcapitalist.com/median-age-changes-since-1950/

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249449/

4. https://www.worldobesity.org/about/about-obesity/prevalence-of-obesity#:~:text=The%20worldwide%20prevalence%20of%20obesity%20nearly%20tripled%20between%201975%20and%202016.&text=If%20current%20trends%20continue%2C%20it,affected%20by%20obesity%20by%202025.

5.https://www.nia.nih.gov/health/heart-health-and-aging

6. https://www.hopkinsmedicine.org/news/newsroom/news-releases/your-weight-history-may-predict-your-heart-failure-risk#:~:text=In%20older%20adults%2C%20study%20finds,for%20weight%20at%20older%20ages.

7. https://www.hindawi.com/journals/crp/2011/134679/