Thinking beyond the tumor to better understand chronic symptoms in breast cancer survivors

Over 200,000 women are diagnosed with breast cancer each year in the United States, and more than 80% are alive 10 years after diagnosis [1]. Treatment generally includes surgery, radiation therapy, chemotherapy, and/or targeted therapies. Choice of treatment is determined by assessing the likely benefit of each therapy for an individual patient, taking into consideration tumor characteristics and likelihood of disease recurrence. Additional personalization of the treatment regimen is generally based on pre-existing patient comorbid conditions, such as heart failure or peripheral neuropathy, which can increase the potential risks of therapy. Most long-term breast cancer survivors recover fully from treatment. However, a substantial proportion experience chronic symptoms, including pain and fatigue, which negatively impact quality of life [2]. The etiology of these symptoms in patients that otherwise remain free from disease recurrence is unclear, especially since all patients typically undergo similar procedures or therapy regimens. Importantly, clinicians are currently unable to accurately predict which patients will experience significant or even disabling long-term toxicity. Identification of patients likely to develop chronic treatment-related toxicities before initiation of therapy would permit a more informed discussion about the risks and benefits of therapy and could guide treatment-decision making. Underlying patient characteristics unrelated to the treatments administered for breast cancer may play a role in the development of chronic pain. For example, an individual’s pain processing systems are responsible for influencing whether or not she perceives pain as well as the level of pain she feels. Some women experience hyperalgesia (increased pain in response to a painful stimulus) or allodynia (pain in response to a normally non-painful stimulus) as has been demonstrated by both patient selfreport and functional neuroimaging [3, 4]. Both hyperalgesia and allodynia can be triggered by a peripheral injury or an inflammatory process, both of which can be present in patients with breast cancer. Moreover, different individuals in the population have markedly different baseline pain and sensory sensitivities, and it appears as though the ones that are the the most sensitive are at the highest likelihood of going on to develop chronic pain following acute pain. Thus, increased pain and sensory sensitivity has characteristics of both a trait that is partly genetically determined (by genes such as catechol-O-methyltransferase, COMT) and a state that can be induced or worsened when there is acute peripheral nociceptive input. Many of our treatments for breast cancer (surgery, radiation, chemotherapy regimens that lead to nerve damage, or endocrine therapies that cause musculoskeletal pain) do induce acute peripheral nociceptive input. Could our treatments for breast cancer, not unlike deployment to war, be a setting where individuals are commonly exposed to a number of painful physical, emotional, and immune stressors? Most will recover following treatment for breast cancer, but some will be left with unresolved pain, fatigue, memory problems and sleep This is an invited commentary to article doi: 10.1007/s10549-011-1757-y