10.5826/dpc.1202a81
Introduction: Psoriasis patients may be susceptible to malignancy due to chronic inflammation. Moreover, biological agents which are used in the treatment of psoriasis might increase the risk of malignancy due to their immunosuppressive effect.
Objectives: We evaluated the mammography results of female patients with psoriasis aged over 40 before the initiation of biological agent treatment. We aimed to determine whether breast cancer screening with mammography should be a prerequisite before the initiation of biological agent treatment for psoriasis.
Methods: Between April 2019 and March 2021, medical records of female psoriasis patients aged over 40 were reviewed retrospectively.
Results: This study included 42 female psoriasis patients (mean age: 53.52±7.09). BI-RADS score was 2 in 18 (42.9%) patients, 1 in 13 (31%) patients, 3 in 9 (21.4%) patients and 4A in 1(2.4%) patient. Isodense masses were detected in 10 (23.8%) patients, while 6 (14.3%) patients had intramammary lymph nodes. Mammography revealed microcalcifications in 6 (14.3%) patients, macrocalcifications in 1 (2.4%) patient and a hamartoma in 1 (2.4%) patient. Isodense masses, calcifications and intramammary lymph nodes were associated with long disease duration (&gt;10 years). Intramammary lymph nodes were more common in patients treated with biological agents previously compared to biologic-naive patients.  
Conclusions: We suggest that female patients over 40, especially who had a long disease duration, family history of breast cancer and previous history of treatment with biological agents should undergo mammography before the initiation of biological agents for the treatment of psoriasis.
text/xml
2160-9381
1935
en
Ayla Gulekon
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
psoriasis
Should Mammography Be a Prerequisite Prior to Initiation of Biological Agents in Patients With Psoriasis?
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-05-02
2021-08-02
2022-05-02
2022-05-24
e2022081
Dermatol Pract Concept
Introduction: Psoriasis patients may be susceptible to malignancy due to chronic inflammation. Moreover, biological agents which are used in the treatment of psoriasis might increase the risk of malignancy due to their immunosuppressive effect.
Objectives: We evaluated the mammography results of female patients with psoriasis aged over 40 before the initiation of biological agent treatment. We aimed to determine whether breast cancer screening with mammography should be a prerequisite before the initiation of biological agent treatment for psoriasis.
Methods: Between April 2019 and March 2021, medical records of female psoriasis patients aged over 40 were reviewed retrospectively.
Results: This study included 42 female psoriasis patients (mean age: 53.52±7.09). BI-RADS score was 2 in 18 (42.9%) patients, 1 in 13 (31%) patients, 3 in 9 (21.4%) patients and 4A in 1(2.4%) patient. Isodense masses were detected in 10 (23.8%) patients, while 6 (14.3%) patients had intramammary lymph nodes. Mammography revealed microcalcifications in 6 (14.3%) patients, macrocalcifications in 1 (2.4%) patient and a hamartoma in 1 (2.4%) patient. Isodense masses, calcifications and intramammary lymph nodes were associated with long disease duration (&gt;10 years). Intramammary lymph nodes were more common in patients treated with biological agents previously compared to biologic-naive patients.  
Conclusions: We suggest that female patients over 40, especially who had a long disease duration, family history of breast cancer and previous history of treatment with biological agents should undergo mammography before the initiation of biological agents for the treatment of psoriasis.
Ayla Gulekon
2022/05/02
10.5826/dpc.1202a81
e2022081
Gazi University School of Medicine Department of Dermatology, Ankara, Turkey
2160-9381
psoriasis
en
e2022081
Should Mammography Be a Prerequisite Prior to Initiation of Biological Agents in Patients With Psoriasis?
https://dpcj.org/index.php/dpc/article/download/1935/1578
        Should Mammography Be a Prerequisite Prior
            to Initiation of Biological Agents in
                   Patients With Psoriasis?
                                                Funda Tamer1, Ayla Gulekon1


1 Gazi University School of Medicine Department of Dermatology, Ankara, Turkey



Key words: biological agents, breast cancer, mammography, psoriasis
Citation: Tamer F, Gulekon A. Should Mammography Be A Prerequisite Prior To Initiation Of Biological Agents In Patients With Psoriasis?
Dermatol Pract Concept. 2022;12(2):e2022081. DOI: https://doi.org/10.5826/dpc.1202a81
Accepted: September 21, 2021; Published: April 2022
Copyright: ©2022 Tamer et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Funda Tamer, Assoc. Prof. MD, Gazi University School of Medicine Department of Dermatology, Ankara, Turkey.
E-mail: fundatmr@yahoo.com




  ABSTRACT             Introduction: Psoriasis patients may be susceptible to malignancy due to chronic inflammation.
                       Moreover, biological agents which are used in the treatment of psoriasis might increase the risk of
                       malignancy due to their immunosuppressive effect.
                       Objectives: We evaluated the mammography results of female patients with psoriasis aged over 40
                       years before the initiation of biological agent treatment. We aimed to determine whether breast cancer
                       screening with mammography should be a prerequisite before the initiation of biological agent treat-
                       ment for psoriasis.
                       Methods: Between April 2019 and March 2021, medical records of female psoriasis patients aged
                       over 40 years were reviewed retrospectively.
                       Results: This study included 42 female psoriasis patients (mean age: 53.52 ± 7.09). BI-RADS score
                       was 2 in 18 (42.9%) patients, 1 in 13 (31%) patients, 3 in 9 (21.4%) patients and 4A in 1 (2.4%)
                       patient. Isodense masses were detected in 10 (23.8%) patients, while 6 (14.3%) patients had intrama-
                       mmary lymph nodes. Mammography revealed microcalcifications in 6 (14.3%) patients, macrocalcifi-
                       cations in 1 (2.4%) patient and a hamartoma in 1 (2.4%) patient. Isodense masses, calcifications and
                       intramammary lymph nodes were associated with long disease duration (> 10 years). Intramammary
                       lymph nodes were more common in patients treated with biological agents previously compared to
                       biologic-naive patients.
                       Conclusions: We suggest that female patients over 40 years, especially those who had a long disease
                       duration, family history of breast cancer and previous history of treatment with biological agents
                       should undergo mammography before the initiation of biological agents for the treatment of psoriasis.




Original Article | Dermatol Pract Concept. 2022;12(2):e2022081                                                                       1
Introduction                                                      premalignant and malignant breast lesions. We aimed to re-
                                                                  veal whether breast cancer screening with mammography
Psoriasis is a chronic inflammatory skin disorder accompa-        should be a prerequisite prior to biological agent treatment
nied by various comorbidities such as psoriatic arthiritis,       for psoriasis or not.
metabolic syndrome and cardiovascular disease [1]. Since
chronic inflammation has been implicated in the etiopatho-
genesis of both psoriasis and malignancy, it has been sug-
                                                                  Methods
gested that psoriasis might be associated with increased risk     Between April 2019 and March 2021, medical records of the
of malignancy. Development of cancer was reported 1.18            female psoriasis patients aged over 40 years who underwent
times more common in patients with psoriasis compared             mammography before the initiation of biological agent treat-
to individuals without psoriasis [2]. Furthermore, mortal-        ment were reviewed retrospectively. Gazi University Ethics
ity rates were elevated in accordance with the severity of        Committee approval was obtained for this study (approval
psoriasis. Malignancies such as squamous cell carcinoma,          number: 2021-412). Patients who had an increased risk for
lymphoma, colorectal, pancreatic, kidney, liver, esophageal       the development of breast cancer such as previous breast
and laryngeal cancer have been related to psoriasis [2]. High     cancer, radiation exposure to the chest, high hereditary risk
prevalence of breast cancer has also been reported in patients    for breast cancer, patients with ovarian and endometrial ma-
with psoriasis [3]. However, relationship between psoriasis       lignancies and immunocompromised patients were excluded
and the risk for the development of malignancy remains con-       from the study. Mammography was routinely performed
troversial [4].                                                   in female psoriasis patients over the age of 40 years before
    On the other hand, increased use of biological agents in      treatment with biological agents for screening premalignant
the treatment of psoriasis leads to concerns about whether        or malignant lesions of the breast. Breast imaging-reporting
biological agents increase the risk of malignancy or not [5].     and data system (BI-RADS) [12], breast density categories,
It has been suggested that tumor necrosis factor-α (TNF-α)        masses, lymph nodes, calcifications and localization of the
inhibitors, anti-interleukin (IL)12/IL-23 and anti-IL-17A an-     lesions were evaluated.
tibodies might increase the risk of malignancies due to their         Statistical analysis was performed using SPSS version
immunosuppressive effects [6]. For instance, use of TNF-α         20.0. Data were represented as mean ± standard deviation
inhibitors such as etanercept, adalimumab and infliximab          (SD) or median for quantitative variables, counts and per-
longer than 12 months has been implicated in increased risk       centage for categorical variables. Differences between two
for malignancy [5]. Development of breast cancer was re-          groups were evaluated by chi-square test. P < 0.05 was con-
ported in a patient following systemic psoriasis treatment        sidered as statistically significant.
with conventional therapy, adalimumab and ustekinumab
[6]. It has been suggested that breast cancer was one of the
                                                                  Results
most commonly detected malignancy in patients who re-
ceived ustekinumab [7]. Biological agent treatment is not         This study included 42 female patients with a mean age of
recommended in patients who had an active malignancy              53.52 ± 7.09 (range: 41-65 years). Thity-two (76.2%) pa-
within the last five years [8].                                   tients had psoriasis vulgaris, 5 (11.9%) patients had palmo-
    Evaluation of patients with psoriasis before and through-     plantar psoriasis and 5 (11.9%) patients had generalized
out the biological agent treatment according to their medical     pustular psoriasis (Table 1). The mean disease duration was
history of cancer and risk for the development of cancer is       17.07 ± 10.99 years (range: 1-47). Twenty-eight (66.7%) pa-
crucial [9]. Therefore, patients with psoriasis receiving bi-     tients did not complain of joint pain, whereas 14 (33.3%)
ological agents should be encouraged to participate in na-        patients had psoriatic arthritis. Past medical history of 16
tional cancer screening programmes [9,10]. However, it has        (38.1%) patients was unremarkable. Ten (23.8%) patients
been reported that patients with psoriasis who were treated       had hypertension, 7 (16.7%) patients had both hypertension
with biological agents did not undergo recommended tests          and type 2 diabetes, 5 (11.9%) patients had type 2 diabetes,
for breast cancer screening adequately despite increased risk     2 (4.8%) had hypothyroidism, 1 (2.4%) had coronary artery
for malignancy [11].                                              disease and 1 (2.4%) had granulomatous mastitis. Only 1
                                                                  (2.4%) patient had a family history of breast cancer.

Objectives                                                            Forty-one (97.6%) patients were treated with conven-
                                                                  tional systemic treatments such as methotrexate, cyclospo-
Within this study, we evaluated the mammography results           rine and acitretin, 7 (16.6%) patients were treated with
of female patients with psoriasis aged over 40 years before       phototherapy and 19 (45.2%) patients were treated with
the initiation of biological agent treatment in order to detect   biological agents, previously. Twenty-three (54.8%) patients



2                                                                     Original Article | Dermatol Pract Concept. 2022;12(2):e2022081
    Table 1. Characteristics and mammography results of female psoriasis patients who underwent
                  mammography before the initiation of biological agent treatment
                                                  Patients with psoriasis (n = 42)
 Mean age (years, ± SD)          53.52 ± 7.09                    (range: 41-65)
 Mean disease duration           17.07±10.99                     (range:1-47)
 (years, ± SD)
 Psoriatic arthritis             Patients with                   Patients without
                                 arthritis 14 (33.3)             joint pain 28 (66.7)
 Comorbidities, n (%)            Patients with           Patients without
                                 comorbidities 26 (61.9) comorbidities 16 (38.1)
 Psoriasis type, n (%)           PV 32 (76.2)                    PPP 5 (11.9)               GPP 5 (11.9)
 Previous treatment, n (%)       Conventional                    Phototherapy 7 (16.6)      Biological treatment
                                 treatment 41 (97.6)                                        19 (45.2)
 Breast density type, n (%)      A 4 (9.5)                       B 24 (57.1)                C 13 (31)                    D 1 (2.4)
 BI-RADS score, n (%)            1 13 (31)                       2 18 (42.9)                3 9 (21.4)                   4A 1 (2.4)
 Isodense mass, n (%)            Patients with IM                Patients without IM
                                 10 (23.8)                       32 (76.2)
 Localization of IM, n (%)       Left breast 5 (11.9)            Right breast 2 (4.8)       Bilateral 3 (7.1%)
 Intramammary                    Patients with ILN               Patients without ILN
 lymph node                      6 (14.3)                        36 (85.7)
 Localization of ILN, n (%) Left breast 4 (9.5)                  Right breast 1 (2.4)       Bilateral 1 (2.4)
 Other lesions, n (%)            Microcalcifications             Macrocalcifications 1      Both micro and              Hamartoma
                                 6 (14.3)                        (2.4)                      macrocalcifications 1 (2.4) 1 (2.4)
BI-RADS = Breast imaging-reporting and data system; GPP = Generalized pustular psoriasis; ILN = Intramammary lymph node;
IM = Isodense mass; PPP = Palmoplantar psoriasis; PV = Psoriasis vulgaris; SD = standard deviation.


were biologic- naïve. Among the patients who were treated                isodense breast masses ranged between 5 to 14 mm. Fur-
with biological agents previously, 13 (31%) patients received            thermore, mammography revealed microcalcifications in 6
anti-TNF-α agents such as infliximab, adalimumab, etaner-                (14.3%) patients, macrocalcifications in 1 (2.4%) patient,
cept and certolizumab pegol, 5 (11.9%) patients received                 both microcalcifications and macrocalcifications in 1 (2.4%)
both anti-TNF-α agents and ustekinumab, and 1 (2.4%) pa-                 patient and a hamartoma in 1 (2.4%) patient.
tient received ustekinumab.                                                    Intramammary lymph nodes were observed in 6 (14.3%)
    Mammographic breast density was type B in 24 (57.1%)                 patients, whereas mamography did not reveal an intramam-
patients, type C in 13 (31%) patients, type A in 4 (9.5%)                mary lymph node in 36 (85.7%) patients. Four (9.5%) pa-
patients and type D in 1 (2.4%) patient. BI-RADS score was               tients had 1 intramammary lymph node, 1 (2.4%) patient had
2 in 18 (42.9%) patients, 1 in 13 (31%) patients, 3 in 9                 2 and 1 (2.4%) patient had multiple intramammary lymph
(21.4%) patients and BI-RADS score was 4A in 1 (2.4%)                    nodes, respectively. Intramammary lymph nodes were local-
patient. No statistically significant association was observed           ized on the left breast in 4 (9.5%) patients and on the right
between BI-RADS score and disease duration or previous bi-               breast in 1 (2.4%) patient. Intramammary lymph nodes were
ological agent treatment (P = 0.51 and P = 0.65, respectively).          detected bilaterally in 1 (2.4%) patient. Moreover, in 1 (2.4%)
The patient with BI-RADS 4A had microcalcifications with                 patient mammography recommended further evaluation of
loose clusters in some areas, and mild pleomorphism in the               an intramammary lymph node on the right breast, which was
upper outer quadrant of the left breast which was revealed to            revealed to be reactive lymph node without an atypical cell.
be nodular adenosis with columnar cell change.                                 The disease duration was less than 10 years in 4 (9.5%)
    Isodense masses of the breast were observed in 10                    patients with an isodense mass of the breast and more than 10
(23.8%) patients whereas mammography of 32 (76.2%)                       years in 6 (14.3%) patients with an isodense mass (P = 0.47).
patients did not reveal a breast mass. Isodense masses were              The disease duration was less than 10 years in 1 (2.4%) pa-
localized on the left breast in 5 (11.9%) patients and on the            tient with calcifications of the breast and more than 10 years
right breast in 2 (4.8%) patients. Moreover, in 3 (7.1%) pa-             in 7 (16.7%) patients with calcifications (P = 0.21). The dis-
tients, isodense masses were localized on the breasts bilater-           ease duration was less than 10 years in 1 (2.4%) patient with
ally. Seven (16.7%) patients had 1 isodense mass, 3 (7.1%)               an intramammary lymph node and more than 10 years in 5
patients had multiple isodense masses. Largest size of the               (11.9%) patients with intramammary lymph nodes (P = 0.41).



Original Article | Dermatol Pract Concept. 2022;12(2):e2022081                                                                          3
    Five (11.9%) patients with an isodense mass of the            it may also be stopped in accordance with the agreement of
breast were treated with biological agents, previously and        both the physician and the patient [15]. However, US Pre-
5 (11.9%) patients with an isodense mass were biologic-           ventive Services Task Force recommends biennial mammog-
naïve (P = 0.72). Three (7.1%) patients with calcifications       raphy screening between the ages of 50 to 74 years [16,17].
were treated with biological agents previously, however, 5        Moreover, National Comprehensive Cancer Network rec-
(11.9%) patients with calcifications were biologic- naïve (P      ommends to start mammography at the age of 40 years and
= 0.62). Five (11.9%) patients with an intramammary lymph         to repeat it every year [15].
node were treated with biological agents previously and 1            Breast cancer has been associated with psoriasis [18]. It
(2.4%) patient with an intramammary lymph node was bio-           has been suggested that the risk of cancer might increase in
logic- naïve (P = 0.04).                                          patients with psoriasis due to chronic inflammation [19]. El-
    In addition, a 58-year-old female patient with a 30-year      evated incidence of psoriasis has also been reported among
history of psoriasis vulgaris and psoriatic arthritis who had     patients with breast cancer [20]. In addition, there are con-
already been diagnosed with breast cancer was determined.         cerns that biological agents may be associated with cancer
Family history of the patient was remarkable for both pso-        development based on their effect on immune system [21].
riasis and breast cancer. The patient was treated with meth-      Since biological treatment has been associated with malig-
otrexate, cyclosporine, acitretin, PUVA and adalimumab,           nancy, it is mandatory to exclude malignancies before the
previously. After 10 months of adalimumab treatment, the          initiation of biological agents and to monitor patients for
patient was diagnosed with grade 1 invasive ductal carci-         cancer development during treatment [22].
noma, therefore adalimumab treatment was stopped.                    Within this study, mammography results of patients with
                                                                  psoriasis over the age of 40 years were evaluated before the

Conclusions                                                       initiation of biological agent treatment. Most of the patients
                                                                  (42.9%) had BI-RADS score 2, which indicated benign find-
Breast cancer is the most frequently detected malignancy and      ings [12]. However, BI-RADS score 3, which indicated prob-
the second most frequent reason of malignancy related mor-        ably benign lesions requiring close follow-up was detected
tality in women globally. Breast cancer is an insidious disease   in 21.4% of the patients [12]. Furthermore, 1 patient had
and it is usually detected by routine screening procedures        BI-RADS score 4A, which indicated 2% to 10% of risk of
[13]. However, recommendations of major guidelines for            malignancy [12]. Isodense masses were detected in 23.8%,
breast cancer screening in the United States differ about the     microcalcifications or macrocalcifications in 19.1% and
initiation age of breast cancer screening with mammography,       intramammary lymph nodes in 14.3% patients. Isodense
screening intervals and when to discontinue mammography           masses, calcifications and intramammary lymph nodes were
[14-17].                                                          more common in patients with history of psoriasis longer
    According to the American Cancer Society, individuals         than 10 years. However, no statistically significant difference
without medical history of breast cancer, BRCA1/BRCA2             was observed between disease duration and the frequency
gene mutation and former radiation treatment to the chest         of isodense masses, calcifications or intramammary lymph
at the age of 10 to 30 years are at average risk for breast       nodes (P = 0.47, P = 0.21, P = 0.41, respectively). On the
cancer. The American Cancer Society recommends to start           other hand, intramammary lymph nodes were more com-
breast cancer screening with mammography for women with           mon in patients who were previously treated with biological
average breast cancer risk at 45 years of age [14]. However,      agents compared to biologic- naïve patients (P = 0.04). In
women aged 40 to 44 years may also undergo mammography            addition, a patient with family history of both psoriasis and
if they request it. The American Cancer Society recommends        breast cancer who had already been diagnosed with breast
to repeat mammography between the ages of 45 to 54 years          cancer while receiving adalimumab was detected. Therefore,
annually and over the age of 55 years biennially. However,        we suggest that female patients over 40 years, especially
women aged 55 years and over may undergo mammography              those who had a long disease duration, family history of
annually if they request. Breast cancer screening should also     breast cancer and previous history of treatment with biolog-
proceed in healthy individuals with life expectancy longer        ical agents, should undergo mammography screening before
than 10 years [14]. Nevertheless, the American College of         the initiation of biological agents for the treatment of psori-
Obstetricians and Gynecologists recommends to start mam-          asis. The limitations of this study were small sample size and
mography at the age of 40 years, however, screening may be        lack of a control group.
initiated between the ages of 40 to 49 years based on shared         British Association of Dermatologists recommends the
decision of the physician and the patient. Individuals should     evaluation of psoriasis patients before the treatment with bi-
repeat mammography every year or biennially. Mammogra-            ological agents according to existing cancer or future malig-
phy is not required in women older than 75 years, however,        nancy risk and thus it directs patients to attend the national



4                                                                     Original Article | Dermatol Pract Concept. 2022;12(2):e2022081
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Original Article | Dermatol Pract Concept. 2022;12(2):e2022081                                                                              5
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