Top 4 Nerve Disorder Side Effects of Breast Cancer Treatment

A variety of upper body pain and function disorders are common in patients treated for breast cancer. Nerve disorder side effects can be some of the most severe and difficult to diagnose, due in part to their broad and variable symptoms. Patient awareness, self-advocacy, and cancer rehabilitation is needed to overcome these side effects and recover quality of life.

Pain and other physical changes and limitations presenting in the chest, back, abdomen, breast and arm are common side effects of breast cancer treatment. The aggressive nature of surgery, chemotherapy, radiation therapy, and hormonal therapies can create significant unintended consequences on normal tissue and body function. These side effects frequently manifest as acute or chronic pain, or functional disorders, that collectively are very common; arm disorders have been reported to affect as many as 7 in 8 women following breast cancer treatment (ref1).

Nerve disorders can hinder a patient’s ability to return to normal activities, and significantly impact quality of life. Common nerve disorders can begin to show symptoms as early as immediately post-operatively or in the first few months following cancer treatment, but some conditions may only appear many years later. Unfortunately there is little general awareness of the breadth of nerve disorders resulting from breast cancer and its treatment, the chronic nature of many of these side effects, nor the impact of them on survivor quality of life.  This is particularly true for newly diagnosed breast cancer patients and their support network of family and friends.

For more side effects of breast cancer treatment, please see: Top 3 Musculoskeletal Side Effects of Breast Cancer Treatment

The major upper body nerve disorders resulting from breast cancer and its treatment are significant, but with appropriate diagnosis and rehabilitation they can be effectively managed or eliminated.

Here I review the top four nerve disorder side effects arising from breast cancer treatment, their causes, their symptoms, and how they can be treated.

1. Chemotherapy-induced peripheral neuropathy

Description and cause:

Damage or dysfunction of the peripheral nerves, known as peripheral neuropathy, is a very common side effect of breast cancer chemotherapy.  Common chemotherapeutic agents used to treat both early and advanced breast cancer have known neurotoxic effects, these include taxanes, vinca alkaloids and platinum analogues (ref2).  These neurotoxic effects result in damage to motor, sensory and autonomic nerves, producing a range of variable symptoms.  Neuropathy due to taxane and vinca alkaloid toxicity appears immediately after exposure to the agent, and is typified by weakness, pain and other sensory changes.  Neuropathy due to platinum agents typically appears later, and can continue to worsen for months following exposure (ref2).

The incidence of chemotherapy-induced peripheral neuropathy depends on the chemotherapeutic agent used.  For example, incidence rates for patients treated with vinca alkaloids is within the range of 30%-47%; for the common taxanes paclitaxel and docetaxel incidence has been estimated to be within the range of 57%-83% and 11-64%, respectively; and for the platinum analogue cisplatin the range is from 28%-100% (ref3).  Risk of neuropathy is believed to be higher in breast cancer patients that have had chemotherapy previously, previous peripheral neuropathy, or radiculopathy (see nerve disorder number 2 below) (ref2).

Symptoms:

The symptoms of chemotherapy-induced peripheral neuropathy typically include severe pain that may be intermittent or constant, and sensory abnormalities such as burning or tingling sensations, loss of feeling (numbness, or loss of sensitivity to temperature and pressure). Difficulties picking up and holding objects with the fingers can also be common. Muscle weakness is not typically associated with this condition. For some, chemotherapy-induced peripheral neuropathy can be progressive and irreversible, while other patients experience improvement of these symptoms over time, in some cases with full resolution.

Diagnosis:

The diagnosis of chemotherapy-induced peripheral neuropathy in the upper body is usually uncomplicated for patients who experience the expected symptoms over the expected time course for the chemotherapy agents they have been treated with. If patients are experiencing abnormal symptoms or the expected symptoms over an abnormal timeline, then alternative diagnoses should be ruled out.

Using patient history, neurological examinations, electrodiagnostic studies and lab testing, a peripheral neuropathy diagnosis can be readily determined for the majority of patients.

Treatment:

Left untreated, chemotherapy-induced peripheral neuropathy is typically progressive, and can be long-lasting or permanent, although in some cases the condition may improve spontaneously.

Treatment of chemotherapy-induced peripheral neuropathy involves education, physiotherapy including exercise therapy, and occupational therapy. Medications can be beneficial for relieving pain and tingling/burning sensations (ref3), but not weakness, numbness or loss of proprioception (perception of the spatial position of the limb). Medications may include local anesthetics, opiods, anticonvulsants and antidepressants.

Improving general health and physical function through exercise may also help improve the symptoms, as well as alternative therapies including meditation, massage therapy, dietary supplements and acupuncture (ref2)

2. Cervical radiculopathy

Description and cause:

Cervical radiculopathy is a nervous system disorder resulting from damage or disturbance of the nerve roots originating in the cervical spine (the neck).  Damage may be caused by nerve compression (a “pinched nerve”) arising from degenerative changes or a ruptured disc, or from tumor growth in this area of the spine.  In cancer patients where symptoms of cervical radiculopathy are worsening, imaging should be immediately performed to rule out tumor growth.

Cervical radiculopathy is relatively common in the general population, and accordingly, most cases in women with breast cancer are unrelated to their cancer or its treatment.  However, peripheral nerve disorders such as radiculopathy can emerge or worsen in response to chemotherapy with neurotoxic agents (ref2).  Cervical radiculopathy is also important in the breast cancer population because it can mimic or exacerbate other cancer related upper extremity disorders.

Symptoms:

The symptoms of cervical radiculopathy are similar to other peripheral nervous system disorders, namely: weakness in the shoulder, arm, and/or hand; and pain, numbness, tingling or burning sensations in the neck, shoulder, arm or hand.

Diagnosis:

Electrodiagnostic testing may be helpful to rule out symptomatically similar brachial plexopathy and peripheral neuropathy disorders.

Treatment:

Treatment of non-tumor related cervical radiculopathy involves physiotherapy and medication with anti-inflammatory drugs. For more advanced cases steroid injections may be beneficial.  Surgical interventions may be considered for some severe cases, although outcomes are mixed (ref4).  Cases of radiculopathy that arise due to tumor growth may require cancer treatment.  Even in these patients, physiotherapy and occupational therapy can be used to increase strength, reduce pain, improve range of motion of the neck and/or shoulder, and increase dexterity and coordination for performing daily activities.

3. Postmastectomy pain syndrome and phantom breast syndrome

Description and cause:

Postmastectomy pain syndrome typically presents as a persistent pain in the chest, armpit, surgical scar, and upper inner arm that continues beyond the normal expected length of time for post surgical pain, in other words, beyond the normal length of time for tissue healing.

Postmastectomy pain syndrome affects somewhere between 4% and 56% of patients, depending on the study and how the condition is diagnosed (ref5). The exact cause of this syndrome is not clear, but it is typically believed to be a result of nerve damage arising from surgery (breast removal or breast reconstruction) or radiation damage, and /or from the developing scar tissue gradually compressing a nerve. Damage to the intercostobrachial nerve is very common during mastectomy (affecting an estimated 20-50% of patients) and may therefore be the most frequent cause (ref6).

Phantom breast syndrome (sensations and/or pain perceived in the breast even though the breast has has been removed), can also be very common in patients who have undergone a mastectomy, and may occur for 10-66% and 0-53% of patients, respectively (ref 7).

Symptoms:

Postmastectomy pain syndrome has been described as a burning, aching or stabbing pain or tightness, which may be exacerbated by movement of the shoulder/shoulder blade. This pain and sensory dysfunction may also contribute to secondary complications such as reduced range of motion in the arm.

Patients with postmastectomy pain syndrome experience symptoms analogous to stump pain in limb amputees, and similarly, they may also experience phantom breast sensations and pain analogous to phantom limb syndrome. Symptoms of phantom breast syndrome tend to occur irregularly, and onset may begin within a few months or years after mastectomy.

Diagnosis:

Pain that is atypical of postmastectomy pain syndrome, or that is progressive in nature, should be investigated to rule out the possibility of tumor recurrence or other complication such as infection or deep vein thrombosis.

Treatment:

Postmastectomy pain syndrome and its complications can be treated through physiotherapy for skin desensitization, range of motion, scar tissue release and strategies aimed at promoting nerve regeneration/healing, as well as pharmaceutically with pain killers and nerve stabilizers.  Treatment strategies for phantom breast pain are the same as for postmastectomy pain syndrome.

4. Brachial plexopathy

Description and cause:

The brachial plexus is a collection of nerve fibers that originates at the spine and travels through the neck and armpit, into the arm. This collection of nerve fibers supplies nerves to the skin and to the majority of the muscles of the arm. Consequently, dysfunctions can result in a wide variety of functional losses and sensation changes.  Brachial plexopathy is a dysfunction of the brachial plexus that may be transient or permanent in nature.  In breast cancer patients brachial plexopathy is most commonly observed as a result of radiation therapy (called “radiation induced brachial plexopathy”) or tumor growth in the brachial plexus region. Neurotoxicity from chemotherapy agents, damage to blood vessels supplying the brachial plexus, and fibrosis (scarring) around the nerves are likely causes of the disorder in this population.

The probability of developing brachial plexopathy increases with the radiation dose per fraction and the total dose received (ref1).  Due to recent improvements in the delivery of radiation therapy, lower dosages are currently in use, and the incidence of this condition is consequently decreasing.  Unfortunately the recent changes to “standard” radiation dosing make it difficult to estimate the current incidence of this condition (ref8), but it is likely that the incidence rate is now near 1%.

Symptoms:

The symptoms of brachial plexopathy are varied, a consequence of the myriad of functions this bundle of nerve fibers controls. In one study, symptoms were found to appear anywhere between 6 months to 20 years after radiation therapy, the median time being 1.5 years (ref9).  Common symptoms may include: pain, loss of sensation, tingling or burning sensations in the arm or hand; weakness in the shoulder, arm and/or hand; or new-onset lymphedema.

Diagnosis:

A clinical assessment including MRI and PET scans can be used to differentiate between brachial plexopathy arising from radiation therapy or from tumor growth. Electrodiagnositc tests may be used to differentiate this disorder from cervical radiculopathy and peripheral neuropathy. Of note, electrodiagnostic tests are not considered to be unsafe for patients with lymphedema (ref10).

Treatment:

Without treatment a sizable proportion of patients suffering from radiation-induced brachial plexopathy will progressively deteriorate to having a limb without mobility or sensation (a “flail arm”), the remaining patients may stabilize, or in some cases spontaneously resolve.  There is no medical cure for brachial plexopathy, but prescription drugs may be beneficial for pain control (ref11). However, early physiotherapy can help prevent muscle atrophy, frozen shoulder syndrome and lymphedema (ref12). Physiotherapy treatment should focus on adaptation and compensation techniques, muscle strengthening, proprioception (perception of the spatial position of the limb) and skin desensitisation.

For more side effects of breast cancer treatment, please see: Top 3 Musculoskeletal Side Effects of Breast Cancer Treatment

References:

1. McCredie M.R., Dite G.S., et al. Prevalence of self-reported arm morbidity following treatment for breast cancer in the Australian Breast Cancer Family Study. Breast 2001;10:515-522.  https://doi.org/10.1054/brst.2000.0291
2. Galecki J., Hicer-Grzenkowicz J., et al. Radiation-induced brachial plexopathy and hypofractionated regimens in adjuvant irradiation of patients with breast cancer – a review. Acta Oncol. 2006;45:280-284. https://doi.org/10.1080/02841860500371907
3. Stubblefield M.D., McNeely M.L., et al. A prospective surveillance model for physical rehabilitation of women with breast cancer: Chemotherapy –induced peripheral neuropathy. Cancer. 2012;118(8 supplement):2250-2260 https://doi.org/10.1002/cncr.27463
4. Stubblefield M.D., Burstein H.J., et al. NCCN Task Force Report: Management of neuropathy in cancer. J Natl Compr Canc Netw. 2009;7:S1-S26. abstract
5. Basho R., Bhalla A., et al. Neck pain from a spine surgeon’s perspective. Phys Med Rehabil Clin N Am. 2011;22:551-555. https://doi.org/10.1016/j.pmr.2011.03.007
6. MacDonald L., Bruce J., et al. Longterm follow-up of breast cancer survivors with post-mastectomy pain syndrome. Br J Cancer. 2005;92:225-230. http://doi.org/10.1038/sj.bjc.6602304
7. Ramesh, Shukla N.K. et al. Phantom breast syndrome. Ind J Palliative Care. 2009;15:103-107. http://doi.org/10.4103/0973-1075.58453
8. Dijkstra P.U., Rietman J.S., et al. Phantom breast sensations and phantom breast pain: A 2-year prospective study and a methodological analysis of literature. Eur J Pain. 2007;11:99-108.  https://doi.org/10.1016/j.ejpain.2006.01.002
9. Stubblefield M.D., Keole N. Upper body pain and functional disorders in patients with breast cancer. PM R. 2014;6(2):170-183. https://doi.org/10.1016/j.pmrj.2013.08.605
10. Fathers E., Thrush D., et al. Radiation-induced brachial plexopathy in women treated for carcinoma of the breast. Clin Rehabil. 2002;16(2):160–5.  https://doi.org/10.1191/0269215502cr470oa
11. American Association of Neuromuscular & Electrodiagnostic Medicine. Needle EMG in certain uncommon clinical contexts. Muscle Nerve. 2005;31(3):398-9.  https://doi.org/10.1002/mus.20238
12. Kori SH. Diagnosis and management of brachial plexus lesions in cancer patients. Oncology (Williston Park). 1995;9(8):756–60. article
13. Schierle C., Winograd J.M. Radiation-induced brachial plexopathy: review. Complication without a cure. J Reconstr Microsurg. 2004;20(2):149–152. https://www.thieme-connect.de/DOI/DOI?10.1055/s-2004-820771