Incidence and Treatment Efficacy of Trigger Finger in the Breast Cancer Population on Aromatase Inhibitors

Background

Stenosing flexor tenosynovitis, more often referred to as trigger finger, is one of the most common causes of hand pain in adults. The reported prevalence in the general population is 2% to 3% and is most common among women in their fifth to sixth decades of life. ¹ Initial management of these patients can involve activity modification, splinting, and judicious use of nonsteroidal anti-inflammatory drugs, but local glucocorticoid injections are the most typical treatment option. Injections can be repeated but are generally limited to 2 or 3 attempts. Surgical release of the first annular (A1) pulley is recommended for patients whose symptoms are refractive to both conservative management and glucocorticoid injections, as is the usual progressive standard of care. ¹

The majority of cases remain idiopathic. ² The main histopathologic change is fibrocartilaginous metaplasia of the ligamentous layer of the tendon sheath at the A1 pulley with secondary reduction in cross-sectional area of the fibro-osseous canal. ³ Current literature illustrates this prevalence is higher in patients with certain comorbidities, including diabetes mellitus, rheumatoid arthritis, and amyloidosis; ⁴ however, limited literature exists implicating whether an estrogen-sensitive receptor and decreased levels of circulating estrogens induced by aromatase inhibitor (AI) therapy result in the development trigger finger. ⁵

In 2015, a case report that described the development of bilateral trigger thumbs in a 49-year old woman who was on antiestrogen therapy with anastrozole was published. ⁶ ERβ, an estrogen receptor that plays a role in inhibiting cell proliferation, has been found abundantly on tenosynovial sheaths. ⁶ It is this limited, yet suggestive research that led us to believe that a correlation exists between the estrogen-depleted states associated with AIs and development of trigger finger. Furthermore, we assert that the patients on antiestrogen therapy are more likely to fail conservative management, consisting of steroid injections, and eventually require surgery.

Methods

A single-center retrospective chart review was conducted after approval was obtained from the institutional review board at the Medical College of Wisconsin. Inclusion was limited to adult patients with a previous diagnosis of breast cancer who were currently on a form of AI therapy. The Medical College of Wisconsin’s I2B2, our institution’s electronic medical record (EMR) cohort-generating search engine, revealed a total of 664 751 patients over the time period from January 1, 2010, through December 4, 2019. This initial study “general” population was then queried using the following diagnoses and/or medications: breast cancer, trigger finger, AI, and diabetes. Of these, 10 029 patients (1.5%) were identified to have a diagnosis of trigger finger, representing our study population. In all, 18 170 patients had a diagnosis of breast cancer, with 3798 on an AI. Development of a trigger finger occurred in 209 patients who were not on an AI and 192 who were on antiestrogen therapy, after excluding those patients who developed a trigger finger before starting the medication (48) or completed therapy before developing a trigger finger (15). In addition, a total of 41 patients were excluded, 22 not on AI and 19 on AI, respectively, secondary to incomplete documentation—most usually, those charts before a transition to an EMR in 2012.

All patients were treated by an orthopedic or plastic surgery–trained hand surgeon (total of 10) at the Medical College of Wisconsin. Specific treatment was under the discretion of the hand surgeon but did follow a protocol generally consisting of glucocorticoid injections being offered and trialed at least once and never more than 3 times before surgical release. All steroid injections involved use of triamcinolone (Kenalog) ranging from 10 to 12 mg mixed with plain lidocaine injected into the flexor tendon sheath. Progression to surgical release or a repeat steroid injection was based on a discussion between the treating surgeon and patient at the time of recurrence of symptoms.

Data collected from these patient encounters included the following: the finger(s) involved, date of first clinic visit and injection, number of injections, handedness, and breast cancer surgery, ± use of radiation therapy, lymphedema, site of breast cancer, start date of AI therapy, length of treatment, and history of diabetes mellitus.

Our primary outcome measures were need for/total number of injections and need for surgery. A χ² analysis was performed to determine significance. A logistical regression analysis was used to evaluate which patient comorbidities were independent risk factors that require surgery as a secondary outcome measure. Significance was determined for a value of P ≤ .05.

Results

Of the 192 patients, 148 (77.1%) required injection. In total, 698 injections were performed on 566 affected fingers, or an average of 1.2 injections per finger (Table 1). A quarter of patients (25.5%) ultimately required surgery, and these patients had more fingers involved (3 vs 2) and more injections per finger (1.5 vs 1) in comparison with those who responded to steroid injections in the cohort, although these increased numbers did not meet significance.

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Table 1.

Characteristics of 192 Patients With Diagnosis of Breast Cancer and Trigger Finger on Aromatase Inhibitor Therapy.

Breast cancer with trigger finger on aromatase inhibitors	Number (incidence)
Total fingers involved	566
Total injections performed	698
Average injections per finger	1.23
Total percent injected	77.1%
Total number requiring surgery	50 (25.5%)
Total number with diabetes mellitus	51 (26.6%)
Total number on radiation	140 (72.9%)
Total number with lymphedema	29 (15.1%)

Compared with the study population (Table 2), patients on an AI for breast cancer were significantly more likely to develop trigger finger (5.3% vs 1.5%; P < .001), require an injection (77.1% vs 56.5%; P < .001), and require surgery (25.5% vs 19.4%, P = .03). This increased likelihood for development of trigger finger (5.3% vs 1.5%; P < .001) and need for injection (77.1% vs 56.5%; P < .001) also became true when comparing our cohort with the control patients not on AIs (Table 3). Although not meeting significance (P = .07), our cohort trended toward requiring surgery more often (25.5% vs 18.1%).

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Table 2.

Comparison Between 3 Main Groups of the Study—General Population and General Population With Trigger, Known Diagnosis of Breast Cancer and Trigger Finger on Aromatase Therapy, and Diagnosis of Breast Cancer and Trigger Finger Not on Aromatase Therapy.

Breast cancer with trigger finger ± AI vs study population
Group	Trigger	No trigger	P value
Study population	10 029 (1.5%)	656 440 (98.5%)	<.001
BCA + TF + AI	192 (5.3%)	3606 (94.7%)
	Injections	No injections
TF in general population	4831 (58.1%)	3480 (41.9%)	<.001
BCA + TF + AI	148 (77.1%)	42 (22.9%)
	Surgery	No surgery
TF in general population	1609 (19.4%)	6701 (80.6%)	.03
BCA + TF + AI	49 (25.5%)	143 (74.5%)
	Surgery	No surgery
TF in general population	1609 (19.4%)	6702 (80.6%)	>.48
BCA + TF	72 (18.0%)	329 (82.0%)

Note. AI = aromatase inhibitor; BCA = breast cancer; TF = trigger finger.

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Table 3.

Comparison Between Patients With Breast Cancer With Known Trigger Finger Who Are on AIs and Not on AIs.

Breast cancer population on AI vs breast cancer population not on AI
Group	Trigger	No trigger	P value
BCA + AI	192 (5.3%)	3606 (94.7%)	<.001
BCA − AI	209 (1.5%)	14163 (98.5%)
	Injections	No injections
BCA + TF + AI	148 (77.1%)	44 (22.9%)	<.001
BCA + TF − AI	118 (56.5%)	91 (43.5%)
	Surgery	No surgery
BCA + TF + AI	49 (25.5%)	143 (74.5%)	.07
BCA + TF − AI	38 (18.2%)	171 (81.8%)

Note. AI = aromatase inhibitor; BCA = breast cancer; TF = trigger finger.

Comorbidities within our study group were common: concomitant radiation therapy (72.9%), diabetes (26.6%), and lymphedema (15.1%). Patients with diabetes and lymphedema had more fingers involved and more injections per finger (Table 4). Despite a higher need for surgery in those with diabetes (51%) and in those with lymphedema (44%) compared with irradiated patients (32%), logistical regression revealed that diabetes (odds ratio [OR], 3.54; P = .01) and radiation therapy (OR, 3.17; P = .02) were the only independent risk factors to require surgery (Table 4).

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Table 4.

Comorbid Characteristics and Comparison of Need for Surgery on Patients With Breast Cancer and Trigger Finger on Aromatase Therapy.

Secondary risk factors	Diabetes	Lymphedema	Radiation
Number	51	29	140
Average number of fingers	2.41	3.03	1.69
Average number of injections	4.16	5.55	2.06
Number requiring surgery	26 (51%)	17 (44%)	44 (31%)
Odds ratio (need for surgery)	3.54	1.86	3.17
Confidence interval (95% lower-higher bound)	1.32-9.45	0.59-5.83	1.24-8.02
P value	.01	.28	.02

Discussion

The treatment of breast cancer was revolutionized by the introduction of hormonal therapy as an adjunct to breast conservation therapy. ⁷ Third-generation AIs are universally used in the treatment of hormone receptor–positive breast cancer. ⁸ These medications have commonly documented side effects, now coined the AI musculoskeletal syndrome, including arthralgias, carpal tunnel, De Quervain tenosynovitis, and stenosing tenosynovitis.^7-12 Despite being commonly cited, the incidence and treatment outcomes for these musculoskeletal issues have yet to be well documented. This study helps to answer some of the questions regarding trigger fingers in this patient population.

The incidence of trigger fingers in our study population (1.5%) is in line with previous epidemiologic studies of the general population, which helps to allow for clinical correlation and generalization. ¹³ In addition, our cohort had a similar incidence of comorbid diabetes as the study population group with trigger fingers (26.6% vs 33.9%). Patients with breast cancer on AI therapy were significantly more likely to develop trigger fingers compared with our population and matched controls. Not only was the incidence increased, but patients were more likely to require and fail injections, ultimately requiring surgery. These results suggest inflammation or overuse is not the sole cause of the triggers, as would likely be the case in the general population. Rather, our findings implicate the low estrogen state induced by AIs in the etiology and treatment resistance of our investigational group.

It is well documented that those with diabetes with trigger finger are at an increased risk of conservative treatment failure,^13,14 also verified in our current cohort. In addition, concomitant radiation was found to be an independent risk factor to require surgery, which is particularly relevant as breast conservation therapy becomes more commonplace. Lymphedema did not increase the risk of surgery—although on investigation of the data, all patients with lymphedema also had radiation therapy. This along with the relatively low number of patients with lymphedema in this study may not provide adequate power for this comorbidity, masking any relative risk effects (Table 4).

Our study does have other limitations, including the retrospective nature of the data collection as well as the lack of a standardized treatment protocol. This study design is essential in epidemiologic studies which can provide insight to help guide treatment options. Although our study does give preliminary information into the treatment of trigger fingers in this population, a future study with a standardized treatment protocol would lend further credence to guide patient discussions.

We did exclude patients who developed a trigger finger before institution of their AI or after they had completed therapy to help limit other confounding variables in these patients. This led to a relatively high number of excluded patients, including those secondary to incomplete patient records (41 of 450, ~10%). This could impact the ultimate findings; however, we do feel that we had adequate patient numbers to make the stated conclusions.

In the future, we are interested to further investigate the patients with similar low-estrogen states, including women with a diagnosis of polycystic ovarian syndrome (PCOS), primary ovarian failure (POF), or endometrial cancer on AI therapy. It will be interesting to see whether an absolute decrease in circulating estrogens (POF) or a relative decrease (PCOS) has an impact compared with a situation in which there is a medication-induced decrease from baseline. This would provide further information on the influence of estrogen receptors in the development and treatment of trigger fingers.

Conclusion

In conclusion, patients with breast cancer on AIs are more likely to have trigger fingers and are more likely to require injections and surgery. Moreover, diabetes and concomitant radiation were each found to be independent risk factors to further increase the likelihood of surgery. These results will help guide treatment discussions in this patient population, especially those with associated comorbidities.