LETTER TO THE EDITOR

Behcet’s Disease and Breast Cancer

To the Editor:

Behcet’s disease (BD) is a systemic vasculitis, char-

acterized by orogenital ulcers, uveitis, arthritis, and

involvement of the gastrointestinal tract, central ner-

vous system, and blood vessels which is frequently

seen in Korea, China, Japan, and Turkey (1). In such

rheumatic diseases, it has been theorized that the fre-

quency of malignancies increase due to the disrupted

immune system and use of immunosuppressive drugs;

a conjecture which has been supported in a few stud-

ies (2). Even fewer studies have looked into the rela-

tionship between BD and malignancies (3). Here, we

present four cases with a history of BD and briefly

review literature pertinent to possible explanations

regarding the connection between autoimmunity and

malignancies.

The first patient is a 49-year-old premenopausal

patient with no predisposing risk factors of breast can-

cer. In 2007, she was diagnosed with BD and has been

using colchicine ever since. Also, in 2007 she had a cyst

excised from her left breast, which turned out to be

benign in the pathologic examination. In March 2011,

the patient presented with a mass in the upper outer

quadrant of the left breast. A biopsy was performed

which revealed signet ring cell carcinoma of the breast.

A modified radical mastectomy was performed. The

pathologic examination revealed a strong ER+, weak

PR+, HER2+, T2N2M0 Grade 2 pure signet ring cell

carcinoma of the breast. Adjuvant chemotherapy con-

sisting of four cycles of adriamycin and cyclophospha-

mide (AC), concomitantly administered with 12 cycles

of paclitaxel and a year of herceptin was initiated.

Radiotherapy is also in the treatment plan.

The second patient is a 45-year-old premenopausal

female with a history of 36 months of oral contracep-

tive use. She was diagnosed with BD at the age of 37

and has been using colchicine ever since. She also has

a history of 20 package years of smoking, and a cyst

excision from the ovary, 12 years ago. The patient

was being followed up for 3 years due to a mass in

the breast via USG when a breast conserving excision

was performed which revealed strong ER, PR+ and

HER2 negative grade 2, T1N0M0 infiltrative ductal

carcinoma in the upper outer quadrant of the right

breast. Adjuvant chemotherapy consisting of six cycles

of tamoxifen concomitantly administered two cycles

of goserelin acetate and a single dose of leuprolide

acetate and radiotherapy was commenced. The patient

did not have any recurrences during follow-up.

The third patient is a 56-year-old postmenopausal

patient with no risk factors for breast cancer which

has been diagnosed with BD for unknown duration of

time. She presented with a mass in the lower outer

quadrant of the breast, from which a biopsy was per-

formed which revealed infiltrative lobular carcinoma

(ILC). Following neo-adjuvant chemotherapy a modi-

fied radical mastectomy was performed which revealed

a strongly ER+, weakly PR+, HER2 negative, grade 2,

T2N1M0 ILC. Adjuvant chemotherapy was initiated

accordingly; the patient is being followed up with no

recurrence.

The last patient that we will take into consideration

is a 51-year-old premenopausal patient with no risk

factors for breast cancer who has been diagnosed with

BD 25 years ago. She has quit using colchicine only

for the past 2 years. She presented with a mass in the

lower inner quadrant of the left breast from which a

biopsy was performed, which revealed a infiltrative

ductal carcinoma. A modified radical mastectomy was

performed. The pathologic examination identified a

ER�, PR+, HER2+ T2N0M0, Grade 3 infiltrative

ductal carcinoma. Adjuvant chemotherapy consisting

of four cycles of AC and five cycles of tamoxifen were

initiated. The patient’s malignancy progressed despite

a multitude of chemotherapy regimens that were

administered, consistent with liver and brain metasta-

sis. Currently the patient is stable and receiving paclit-

axel and trastuzumab with signs of regression in the

brain metastasis.

A single center study conducted in Korea has iden-

tified three patients out of 1,769 who have concurrent

breast cancer and BD (3). We have four patients of

Address correspondence and reprint requests to: Emir Charles Roach,

MD, Cleveland Clinic – Pathobiology, 9500 Euclid Avenue, Cleveland, OH

44106, USA, or e-mail: roache@ccf.org

DOI: 10.1111/tbj.12320

© 2014 Wiley Periodicals, Inc., 1075-122X/14The Breast Journal, Volume 20 Number 5, 2014 566–567

2,006 breast cancer patients as such. It has been

reported that due to a polymorphism of TGF-b recep-

tor gene in BD may have a protective role in develop-

ment of malignancy (4). Conversely, however, small

vessel vasculitis are known to increase the risk of

malignancies (5). Other solid cancers associated with

BD are bladder, uterus, thyroid, and stomach cancer

(6). The relationship between BD and breast cancer

remains controversial at best. Large scale, multicentric

studies ought to be conducted to firmly establish the

relationship between these two pathologies.

Emir Charles Roach, MD*

Ibrahim Petekkaya, MD†

Kadri Altundag, MD†

*Department of Pathobiology

Cleveland Clinic

Cleveland

Ohio

and †Institute of Oncology

Hacettepe University

Ankara

Turkey

REFERENCES

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2. Szekanecz Z, Szekanecz E, Bak�o G, et al. Malignancies in auto-

immune rheumatic diseases - a mini-review.Gerontology 2011;57:3–10.3. Ahn JK, Oh JM, Lee J. Behcet’s disease associated with

malignancy in Korea: a single center experience. Rheumatol Int2010;30:831–5.

4. Kaklamani VG, Sadim M, Koumantaki Y, Kaklamanis P,Pasche B. Role of polymorphisms in adamantiades—Behcet’s dis-

ease. J Rheumatol 2008;35:2376–8.5. Pankhurst T, Savage CO, Gordon C, Harper L. Malignancy

is increased in ANCA-associated vasculitis. Rheumatology (Oxford)2004;43:1532–3.

6. Kaklamani VG, Tzonou A, Kaklamanis PG. Behcet’s disease

associated with malignancies. Report of two cases and review of the

literature. Clin Exp Rheumatol 2005;23:S35–41.

Letter to the Editor • 567