Spinal cord injured women’s treatment of breast carcinoma: alert to complications

ABSTRACT INTRODUCTION Women with spinal cord injury (SCI) and who develop breast cancer are a vulnerable and potentially overlooked population. They experience risk factors owing to

decreased mobility and are at risk for unique complications from their oncologic treatment. CASE PRESENTATION A 54-year-old woman who suffered a T6 AIS A traumatic SCI in 1981, who was

diagnosed 32 years later with estrogen receptor and progesterone receptor positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma. During the course of her

chemotherapy, she experienced several complications, including reflexive diaphoresis, urinary tract infection, leukopenia, anemia, dehydration, and weakness. These contributed to the

development of a stage 4 ischial pressure sore, which required complex treatment. DISCUSSION There is a paucity of literature examining the complications of chemotherapy that may be unique

to those with SCI. Physiatrists will be seeing more women undergoing oncologic care, as this population of patients ages. A multidisciplinary approach that takes into account the

pathophysiologic changes associated with SCI is crucial to understand and prevent complications that could affect their outcomes and contribute to increased cost in a value-based health-care

system. You have full access to this article via your institution. Download PDF SIMILAR CONTENT BEING VIEWED BY OTHERS A PERSPECTIVE ON ADVERSE HEALTH OUTCOMES AFTER BREAST CANCER TREATMENT

IN WOMEN WITH SPINAL CORD INJURY Article 07 April 2021 DUAL LESION SPINAL CORD INJURY IN A POLYTRAUMA PATIENT: A CASE REPORT Article 30 September 2021 LONG-TERM OUTCOME FOLLOWING SURGICAL

TREATMENT OF POSTTRAUMATIC TETHERED CORD SYNDROME: A RETROSPECTIVE POPULATION-BASED COHORT STUDY Article Open access 19 January 2022 INTRODUCTION Since the 1980s, the life expectancy for

persons with traumatic paraplegia who survive 1 year after injury has been ~ 59–76.4% of the life expectancy of people without an spinal cord injury (SCI) [1]. As medical interventions

continue to improve, it is reasonable to expect that physiatrists will see an aging population of persons with SCIs. In general, research on SCIs has a tendency to focus on the course and

outcomes primarily of men, compared with women, as ~ 80% of new SCIs occur in males [1]. However, several authors have noted that when examining the gender distribution of persons with

spinal cord injuries, there appears to be a more bimodal pattern, with incidence increasing among women over the age of 60 [2]. Still, because the overwhelming majority of SCI cases occur in

men, the unique issues experienced by women with SCI are at risk for being overlooked. It is reasonable to assume that women aging with SCIs will be subject to differences in complications

and risks compared with men. One issue of particular interest is breast cancer, as it is the most commonly diagnosed cancer among women [3]. An extensive PubMed review of the literature

utilizing search terms that included “spinal cord injury”, “pressure injury”, “pressure ulcer”, “chemotherapy”, “breast cancer”, “disability”, “mobility” resulted in several studies that

examined the barriers women with SCI and other physical disabilities have faced during the receipt of routine preventative care. This included difficulties with access and incomplete

evaluations owing to an inability to accommodate their functional limitations [4, 5]. However, once diagnosed, most studies focused on the relationship between functional needs and surgical

intervention in persons with SCIs. There has only been one qualitative study examining quality of life and concerns expressed by this dually diagnosed population and there remains a paucity

of data examining the potential adverse effects of medical oncologic treatments in persons with SCI. [6] One goal of this paper is to further discuss how pathophysiologic changes associated

with SCI can impact treatment and outcomes. Decreased mobility can result in an increased risk of venous thromboembolism, falls, pressure injuries, and infections. Pressure injuries, defined

as a lesion on any skin surface, resulting from pressure or pressure in combination with shear force and/or friction, are a potentially deadly and costly complication of spinal cord

injuries. According to the Agency for Healthcare Quality and Research, in the United States, it is estimated that the cost of care for pressure ulcers is up to $11 billion annually [7]. The

incidence of pressure ulcers in the SCI population is 25–66% [8]. Several factors that confer increased risk of pressure ulcers in persons with SCI include decreased/absent protective

sensation, increased risk of insulin resistance leading to diabetes, anemia, impaired mobility, and malnutrition [9, 10]. Prevention of these injuries is a lifelong effort for those living

with SCIs and their caregivers. Prevention of pressure injuries has been shown to cost less than management of the injuries themselves, as would be expected owing to decreased

hospitalization for pressure injury and related complications [8]. This case provides a unique opportunity, as this individual not only has a 35-year history of traumatic paraplegia, but is

also a nurse who has worked primarily with persons with SCI during her career, who had managed to mitigate many of the risks associated with her SCI. Despite her medical training and

background knowledge, during her breast cancer treatment, she developed a complex Stage 4 pressure injury to her left ischial tuberosity, which ultimately required surgical reconstruction.

The goal of the discussion is to understand the factors that contributed to the development of the pressure sore and determine potential methods to prevent the development of pressure injury

in persons with SCIs undergoing cancer treatment. CASE PRESENTATION N.S. is a 54-year-old woman diagnosed in 1981 with T6 AIS A traumatic paraplegia. Since then, she had been functioning

independently at a primary wheelchair level. Her past medical history consisted of her SCI, hypertension, neurogenic bladder with chronic indwelling Foley, autonomic reactions to bladder

stones, and neurogenic bowel. Of note, she had previously suffered from a pressure injury on her left ischial tuberosity immediately after her injury, with recurrence in 2010. In December

2014, during a screening mammography, the woman was found to have a calcification in her right breast. In January 2015, a biopsy revealed moderately differentiated invasive ductal carcinoma,

estrogen receptor/progesterone receptor (ER/PR) positive and human epidermal growth factor receptor 2-/neu negative. At the end of January 2015, a right breast segmental resection and

sentinel lymph node dissection revealed poorly differentiated invasive ductal carcinoma with two negative sentinel lymph nodes, and an involved superior margin (pT1c (1.5 cm) N0, Stage I).

She had additional margins resected in the beginning of February 2015. She had an Oncotype Dx, which is a prognostic tool that evaluates 21 genes by reverse transcriptase

polymerase-chain-reaction. The results of this test have been prospectively validated and can quantify the likelihood of distant recurrence as well as predict benefit from adjuvant

chemotherapy in women with ER positive, node-negative breast cancer. [11,12,13] Her Oncotype Dx score was found to be in the high range at 36, which translated into a 24% chance of distant

recurrence in 10 years after 5 years of Tamoxifen treatment. In early 2015, two therapeutic chemotherapy options were recommended based on her Oncotype Dx score: dose dense Adriamycin and

Cytoxan over every 2 weeks for four cycles, followed by four cycles of dose dense Taxol or Taxotere and Cytoxan once every 3 weeks for 6 cycles as an alternative. Owing to the risk of

neuropathy with Taxotere, the woman and her oncologist decided to proceed with Adriamycin and Cytoxan, followed by Taxol. Retaining functional independence and quality of life were

considered priorities by the woman. By April 2015, the woman had received three cycles of her chemotherapy regimen, and had some difficulty tolerating the treatments. During her second cycle

of chemotherapy, she developed a urinary tract infection (UTI) requiring antibiotics, and a noticeable increase in sweating in her lower extremities, resulting in dehydration requiring

intravenous fluid administration. She also had leukopenia and anemia with a hemoglobin of eight requiring two blood transfusions. She noticed an increase in spasticity and muscle spasms.

Further, she reported a folliculitis type rash that developed on her lower extremities. During this time, she also noted an area of non-blanching erythema over her left ischial tuberosity.

This was likely a Stage 1 injury at this point [14]. Soon after her third cycle of chemotherapy, two wounds developed and within a few days, progressed to Stage 3. She made an appointment at

this time to be seen by her SCI trained physiatrist and a comprehensive wound care team. Considering her wounds and her functional ability, it was decided that she would discontinue her

treatment with Adriamycin and Cytoxan, and transition to 30 treatments of adjuvant radiation therapy, followed by 5 years of treatment with daily oral Arimadex. She was not able to complete

her chemotherapy regimen. She is currently in remission. Her wound care team placed her on bedrest with limited sitting. Despite regular follow-ups at weekly intervals, her wounds, initially

measuring 15 × 12 × 1mm and 19 × 25 × 2mm had increased in size and coalesced. A fibrotic area was debrided, and they were found to have progressed to Stage 4 injuries. By May 2015, she

showed some signs of induration and erythema which was treated with Bactrim double strength for 1 week. After treatment with antibiotics, she was examined on monthly intervals by wound care,

and was able to start a seating protocol. She was able to return to work on a limited basis by September 2015. By October 2015, unfortunately, the wound progressed with increased

undermining. The woman was placed back on bedrest, and surgical consultation was obtained. A wound vacuum-assisted closure therapy was used for 4 months. She continued to receive local wound

care from both her surgeon and physiatry, but ultimately required extended hospitalization, with partial ischial resection for osteomyelitis and left posterior proximal thigh myocutaneous

V–Y advancement flap closure of her wounds in September 2016. After surgery, she was admitted to acute inpatient rehabilitation. Unfortunately, this stay was cut short due to complications

with her bowel function. She eventually returned to acute inpatient rehabilitation later in September. There she was treated for 2 months. She was able to advance through a sitting protocol

and return to her previous modified independent level of function for ADLs, transfers, and mobility at a power wheelchair level. Although typically patients are initially transferred to a

skilled facility for bedrest after these types of surgeries prior to being admitted to an acute rehab facility to progress through a seating and then mobilization protocol, some people are

able to be admitted directly into this acute inpatient rehabilitation facility immediately after surgery, owing to a contractual agreement where the facility is reimbursed at a “wound care

rate”, which is lower than their typical rate. During her rehab stay, she was evaluated by Orthopedics and Plastic Surgery, who noted that she was healing well from her ischial resection,

and her flap was viable without evidence of new skin breakdown. DISCUSSION Increased risk of pressure injury in persons living with SCI is owing to several underlying changes in

pathophysiology. In general, the older the person is post SCI, the greater risk of developing an ulcer, with up to 80% of persons living with SCI developing a pressure ulcer during their

lifetime [15]. Shear and pressure, combined with a lack of protective sensation are the primary cause of pressure injuries. In the case of this individual, increased weakness following UTI

as well as chemotherapy may have contributed to increased shear with transfers, as well as reflexive diaphoresis. Moisture as a result of sweating may have contributed to skin maceration and

evolution of her pressure injury. This woman also had a history of previous pressure injury to the same area. In a study of veterans with spinal cord injuries, previous injury has been

shown to increase risk for repeat injury [16]. In a review of the pathophysiologic changes experienced by denervated tissues after SCI, Rappl evaluates how an impaired wound-healing cascade

can impact healing [17]. During the inflammation phase, typically cellular components enter the wound space with the goal to protect and heal by delivering essential enzymes, nutrients, and

oxygen. This requires increased vasodilation. However, after an SCI, vasomotor pathways are injured, impacting the sympathetic nervous system, whereas sparing the parasympathetic system

[17]. This has been described to occur from levels above T6, to levels above L2 [18,19,20]. This results in a loss of tone below the lesion, with a state of generalized vasodilation. There

is also decreased density in both alpha and beta adrenergic receptors in insensate skin in older injuries, which are involved in adjusting vascular reactions [17]. Because there is baseline

vasodilation, there is no way to further increase vasodilation, impairing the ability to mount an inflammatory response [17]. This vasodilation also contributes to decreases in both systolic

and diastolic blood pressure. This impairs perfusion and delivery of nutrients and oxygen to the tissues impairing epithelial cell activity across the wound bed as well as affecting

angiogenesis [17]. Building collagen during initial closure and remodeling is therefore impaired. This is further exacerbated by the fact that persons with SCI experience significant

collagen catabolism in non-injured insensate tissue. An inability to transport appropriate amino acids and enzymes to the wound results in decrease collagen synthesis, with resulting

collagen being of poorer quality [17]. The primary treatment, which this woman received, is bedrest to distribute pressure more evenly across the location of the wound. Immobilization

promotes further collagen breakdown and metabolism as well as decreases the already impaired perfusion of tissues [17]. Persons with SCI also experience significant muscle atrophy below the

level of injury, resulting in more protuberant bony prominences at high risk for injury. Atrophy and weight loss can be exacerbated during chemotherapy owing to common side effects of nausea

and vomiting, which can result in malnutrition. Weakness and fatigue can also affect the ability to transfer, resulting in more dragging and shearing during the process. Increased risk of

infection, accompanied by sweating, can prolong and complicate wound healing [21, 22], whereas myelosuppression accompanying chemotherapy can further compromise an individual’s ability to

heal. There were several other important aspects to note in this case. The pressure ulcer was in the same location as a prior lesion. Because the collagen synthesized after injury is of

poorer quality, people are at risk for recurrent ulcer. Patterns of recurrence suggest this nature of incomplete or suboptimal healing of initial pressure injuries [16, 23]. It is important

for providers treating persons with SCI to be aware of any history of previous pressure injury in order to promote more frequent surveillance and ensure early involvement of physiatry and

wound care. This woman also experienced what was described as significant reflex sweating, likely multifactorial owing in combination to adverse effects from her chemotherapy regimen acting

as an irritant and the urinary tract infection she sustained. Sweat glands derive innervation from the sympathetic nervous system, with structures extending from T1–L2 controlled by centers

in the hypothalamus. Injury to the cord can affect supraspinal control of these functions [24]. Reflex sweating can occur as a result of afferent stimuli from below the level of injury—in

this case the wound and urinary tract infection could have precipitated reflex sweating. Management of hyperhidrosis is essential in the setting of pressure injuries, as excess moisture can

contribute to skin breakdown, not to mention intravascular depletion with further compromise of the ability to perfuse the wound bed [25]. For persons with SCI undergoing oncologic care, a

comprehensive rehabilitation team with wound care and therapy can help mitigate some of the risk factors that can be exacerbated during their treatment [26]. For pressure ulcers, immediate

treatment is essential to prevent progression and promote healing. Physiatrists can offer offloading recommendations and ensure appropriate equipment to offload pressure to vulnerable areas,

including seat cushions, wheelchair evaluations, as well as evaluate for the need for specialized equipment such as low air loss mattresses [26]. In this case, early evaluation and

replacement of this individual’s wheelchair cushion would have helped prevent the development of the pressure sore. Regular follow-up with wound-care nursing as a part of the rehabilitation

team can ensure that people receive adequate local treatment and protection for the wound. Dietitians can ensure the individuals are able to get adequate nutrient supplementation during

their treatment. Once appropriate, therapy can help strengthen and improve functional transfers and bed mobility to minimize shear. It is important to note that comorbidities associated with

aging in persons with spinal cord disease can result in further declines in mobility and in complications associated with immobility, such as pressure injuries, infection, and falls/injury.

This is regardless of gender or ethnicity. Pressure injuries can significantly impact not just health care utilization and spending, but also peoples’ quality of life, pain levels,

independence, and earning potential. The individual in this scenario missed a significant amount of work while receiving treatment. It’s estimated that 25% of total lifetime health care

costs are related to pressure injuries for persons with SCI [21]. The risks of pressure injury in individuals with SCI are clear, with 7–8% of deaths in SCI being due to complications of

pressure injury [21]. People with spinal cord injuries undergoing chemotherapy are particularly at risk due to complications of myelosuppression, steroid use, malnutrition, increased risk of

infection, as well as potential complications of autonomic dysreflexia and reflex sweating contributing to skin maceration. For the health care system, the cost of individual patient care

ranges from $20,900 to $151,700 per pressure ulcer, with each ulcer adding $43,180 in costs to a hospital stay [7]. There is a paucity of literature examining the complications of

chemotherapy that may be unique to those with SCI. By addressing medical complications that can contribute to pressure injuries, physiatrists can be instrumental in preventing their

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received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Thomas Jefferson University Hospitals,

Department of Rehabilitation Medicine, Philadelphia, PA, USA Ashley L. de Padua & John F. Ditunno Jr. * Thomas Jefferson University Hospitals, Department of Hematology and Medical

Oncology, Philadelphia, PA, USA Kimberly Strickland * Main Line Health, Radnor, PA, USA Mary Patrick * Sidney Kimmel Medical College, Philadelphia, PA, USA John F. Ditunno Jr. * Regional

Spinal Cord Injury Center of the Delaware Valley, Philadelphia, PA, USA John F. Ditunno Jr. Authors * Ashley L. de Padua View author publications You can also search for this author inPubMed

 Google Scholar * Kimberly Strickland View author publications You can also search for this author inPubMed Google Scholar * Mary Patrick View author publications You can also search for

this author inPubMed Google Scholar * John F. Ditunno Jr. View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Ashley

L. de Padua. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE de Padua, A.L., Strickland, K., Patrick, M. _et al._ Spinal cord injured women’s treatment of breast carcinoma: alert to complications. _Spinal Cord Ser Cases_ 4, 46 (2018).

https://doi.org/10.1038/s41394-018-0079-2 Download citation * Received: 04 March 2018 * Revised: 10 April 2018 * Accepted: 15 April 2018 * Published: 23 May 2018 * DOI:

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