Timothy P. Dougherty

Background: The change over time of certain inflammatory markers, such as the neutrophil–lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI), is a prognostic factor in many cancers, including breast cancer. This study retrospectively evaluated how a 12-week intensive exercise program might have influenced both the NLR and SIRI in women with breast cancer. Methods: Two institutional review board-approved prospective clinical trials, EXERT-BC (NCT05747209, 2 November 2022) and EXERT-BCN (NCT05978960, 31 July 2023), were retrospectively assessed. Complete blood count (CBC) values performed before and after participation in a 12-week intensive resistance program were analyzed post hoc. Blood tests were ordered as part of routine clinical care and not pre-specified by either study protocol. Participants who had blood work more than four months from study intake or completion were excluded. Additionally, those undergoing active systemic therapy or with underlying inflammatory conditions were also excluded. The NLR and SIRI values were analyzed via the Mann–Whitney test, with pair-wise assessment of pre- and post-intervention values via the Wilcoxon signed-rank test. Results: Out of 84 participants, 21 people met the inclusion criteria. Roughly 70% had either ductal carcinoma in situ (DCIS) or early-stage breast cancer. The average blood draw was taken within two months of study intake and outtake. After the 12-week structured exercise program, there was an associated reduction in both the NLR (2.26 [IQR, 1.70–4.22] to 1.99 [1.44–2.62]; ΔNLR = −0.27, W = 47.0, p = 0.016) and SIRI (1.23 [0.82–1.64] to 0.80 [0.59–1.45]; ΔSIRI = −0.43, W = 48.0, p = 0.018). Of those who saw their inflammatory markers improve, roughly two thirds showed a clinically relevant improvement. Conclusions: Completion of a 12-week intensive resistance exercise program was associated with a statistically improved NLR and SIRI. The small sample size and retrospective nature limit the broader application of these findings. The results, however, provide a genesis for prospective validation examining the potential benefit exercise might have on the NLR and SIRI in women with breast cancer.

“What do you do?” “I work with people who have cancer.” “That must be difficult.” It has been surprising how many times I have had some version of that conversation. Before residency and even throughout medical school, the thought that working with patients with cancer must be difficult did not really cross my mind. Only after hearing these sentiments over and over again at cocktail parties, weddings, and even family gatherings did I start to reflect on what a profession in oncology meant for myself and for those around me. And, for the most part, people are right. Working with patients with cancer is difficult. There is participation in multidisciplinary decisions, new consultations, radiation planning (I am a radiation oncologist), treatment-related adverse effects, follow-up care, the delivery of bad news, the death of a patient. However, I have found that the point of view implied by the word “difficult” is potentially different than my own definition. I have come to interpret others’ use of the word as a synonym for dealing with extreme sickness and ultimately death. “That must be difficult… [because you work with people who are sick and dying].” This can surely be true. Cancer is a horrible disease that can cause pain, discomfort, adversity, and death. And seeing those things in another human being can be challenging and difficult to experience.

Many cancers are associated with poor diet, lack of physical activity, and excess weight. Improving any of these three lifestyle factors would likely reduce cancer deaths. However, modifications to each of these—better nutrition, enhanced activity and fitness, and loss of extra body fat—have different effect sizes on cancer mortality. This review will highlight the relative benefit that each lifestyle change, enacted prior to a diagnosis of cancer, might impart on cancer-related deaths, as well as attempt to quantify the changes required to derive such a benefit. The review relies primarily on epidemiological data, with meta-analyses serving as the backbone for comparisons across interventions and individual studies within the larger meta-analyses providing the data necessary to form more quantitative conclusions. The reader can then use this information to better understand, recommend, and implement behaviors that might ultimately reduce cancer mortality. Of all the interventions, it seems clear that exercise, specifically improving cardiorespiratory fitness, is the best way to decrease the risk of dying from cancer.