Crucial Answers on Long-Term Physical Health Effects From Breast Cancer Treatments

Clara Bodelon, PhD, MS, discussed her recently published study which found that the greatest physical health declines in patients who survived breast cancer stemmed from chemotherapy.

Clara Bodelon, PhD, MS, senior principal scientist of survivor research at the American Cancer Society, spoke with CancerNetwork® about a study she published in JAMA Network Open that reported chemotherapy leads to more significant long-term health declines compared with endocrine therapy in the treatment of breast cancer.

The study found that the greatest decline of physical health observed was with chemotherapy and endocrine therapy combined as a treatment (β = −1.34; 95% CI, −2.07 to −0.61) then chemotherapy (β = −1.20; 95% CI, −2.32 to −0.07) and finally endocrine therapy (β = −0.40; 95% CI, −0.94 to 0.14).

Bodelon stated that it was well known that women who received breast cancer treatment experienced greater physical health declines than those who did not, but there were not an extensive number of studies that showed which therapies had the most meaningful declines. These results show that patients who were treated with chemotherapy will experience more difficulty doing daily tasks and will deal with more pain and fatigue.

Additionally, tamoxifen did not show any notable decline in physical health as an endocrine therapy whereas aromatase inhibitors accounted for all the decline seen. Due to the amount of data, they had on this subject, Bodelon spoke to a need for further research on this topic so that physicians can be made more aware of the effects of the medications they prescribe.

There are still many more avenues stemming from this study that need to be evaluated, and Bodelon urged professionals in the health care field to pay more attention to the long-term health outcomes, as well as the short-term.

CancerNetwork: Why did you choose to research the long-lasting physical health effects of chemotherapy and endocrine therapy?

Bodelon: There have been well-designed studies that have looked at the long-term effects of physical health decline among cancer survivors in general, and breast cancer survivors. One of the things that we have seen is that all cancer survivors, and in particular breast cancer survivors, have a [physical health] decline compared with similar women of the same age. It’s thought that it’s due to the cancer and the cancer treatments, but it has been a general view [held about] the cancer survivors, and we wanted to specifically look at the different treatments that women with breast cancer will receive and see whether we saw the same effects dependent on the treatment that they received.

What do these results mean?

For women who received chemotherapy, what we saw is that they have long-term effects within the first 2 years after a cancer diagnosis, 2 to 5 years [after the diagnosis], and more than 5 years after the cancer diagnosis, and we saw that, compared with women who are cancer-free of the same age, they have declines in their physical health. However, in the women who received endocrine therapy, we saw that, after the first 2 years, the physical health was similar to women who are cancer-free of the same age, suggesting that those who receive endocrine therapy do not have long-lasting effects. At least with the physical health aspects like physical functioning, they may be similar to those who never had cancer to start with.

What does physical health mean in relation to this study?

Physical health is the aspect of health that is not mental health. What that includes is the ability to move, the ability to get dressed and bathe yourself, not having pains, and not having fatigue—so everything in health that is not mental health. What we see is that, as we age, some of these aspects may be declining, and so older people may have some pains, they may have some fatigue, and they may not be able to, [when they are] 80 to 90 years old…do all the activities of daily living. What we wanted to see is if cancer survivors of younger ages had those abilities [and if] they could do those types of things similar to cancer-free women of a similar age.

For those who did have endocrine therapy, they did have those abilities, similar to the women who were cancer-free, but not with those who received chemotherapy. What is important is that before we saw cancer survivors as a whole and not specifically across treatments, but [here] we saw a difference in treatment. One of the big topics in oncology is the escalation of treatment, and as we learn what the specific treatments are…and as we personalize the treatments, the consequences of the treatments may be different, so this is a way for us to understand what those outcomes are.

Are there any implications from chemotherapy showing the most significant mental health declines?

The implication is that we need to inform patients, as well as primary care physicians, because someone could receive chemotherapy or a combination of chemotherapy with endocrine therapy, but as long as they have chemotherapy, it doesn’t matter if they have other treatments, they may suffer this decline. It may inform physicians that these women may need help long term, going to physical therapy, for instance, and having it as part of their health care plan. They need these providers to help them offset some of the consequences of the treatment. That may not be the case for endocrine therapy. It may be that some women still need it, but because cancer care is expensive, we need to understand who the ones that need it the most [and we need] to understand how we change treatments and what the consequences are. Our study starts shedding some light into that.

What does it mean that tamoxifen didn’t show notable declines in physical health, but other endocrine therapies did?

The numbers [on why tamoxifen didn’t show a notable decline in physical health] were small, so we want to continue in the future looking more into that, but tamoxifen has shown in other studies that the consequences—the long-term effects—of tamoxifen may differ…and they may not have an increased risk of cardiovascular disease among women that take tamoxifen, for instance. With aromatase inhibitors, this is less clear. We wanted to distinguish those 2 because the mechanisms of action of these 2 drugs differ. It seems like…because…clinical trials have shown a better outcome on recurrences with aromatase inhibitors, it’s possible that women who receive endocrine therapy may start receiving more aromatase inhibitors. We need to understand what the consequences [are]. The physician needs to understand what all the consequences of these drugs [are] and what the long-term effects [are]. It’s additional information that the physicians need to take care to account [for].

What impact do you think this study will have on clinical practice and patient care for breast cancer survivors going forward?

The idea is that the patients are informed of the long-term consequences [of the treatments] so they can have some [input in] decision making, as well as [making sure the] primary care physicians and the entire cancer care team are knowledgeable about the long-term consequences of each treatment, and they can make the appropriate decisions for each woman.

What are some of the next steps for research?

We are going to be looking at other treatments that breast cancer survivors receive, and at the types of chemotherapy they receive. [We’re going to] look into longer-term effects, like mortality. We’re also going to look into lifestyle factors. If someone who is obese receives endocrine therapy, does it have the same effects as [it would on] someone who is lean and receives endocrine therapy? … [We want to] inform the women themselves on the things that they can do, like if they’re smokers or if they are not smokers, and how that can affect the long-term effects. Those are things that we plan to study again, continuing to inform the women as well as physicians, as to what the benefits for them are [with each therapy].

What are some of the key takeaways for your colleagues and other physicians?

We are starting to try to think about personalized medicine and long-term outcomes—it’s going to be a consequence of that personalized medicine. Not all breast cancer survivors are the same and not all necessarily need the same care. We see that those taking chemotherapy are going to be the ones that are going to require the most help, and we need to understand if all chemotherapies are going to be the same, but [the care that these women receive] is going to have to be individualized.

Also, have a bright side. We think of breast cancer as very grim news—having breast cancer or cancer in general—but certain treatments are improving greatly, and certain treatments may not have the long-term effects that many breast cancer survivors had in the past. They are becoming better, and they have much less adverse effects.

Reference

Bodelon C, Masters M, Bloodworth DE, et al. Physical health decline after chemotherapy or endocrine therapy in breast cancer survivors. JAMA Netw Open. 2025;8(2):e2462365. Published 2025 Feb 3. doi:10.1001/jamanetworkopen.2024.62365