A case of a trans‐masculine patient receiving testosterone with a history of estrogen receptor‐positive breast cancer - Eckhert - 2020 - The Breast Journal - Wiley Online Library

10/15/2020 A case of a trans‐masculine patient receiving testosterone with a history of estrogen receptor‐positive breast cancer - Eckhert - 2020 - The Breast Journal - Wiley Online Library

The Breast Journal / Volume 26, Issue 9

COMMENTARY

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A case of a trans‐masculine patient receiving testosterone with a history of estrogen receptor‐positive breast cancer

Erik Eckhert MD, MS , Benjamin Laniakea MD , Allison W. Kurian MD, MSc

First published: 07 April 2020

https://doi-org.ezproxy4.library.arizona.edu/10.1111/tbj.13829

Breast cancer occurs in 10% of women and <0.1% of men in the United States. But because gender identity is not reported in cancer registries,

there are only 22 reported cases of breast cancer in transgender men.1-4 A recent Dutch cohort study found that transgender men have a 60‐

fold higher incidence of breast cancer compared to cisgender men and a 5‐fold lower incidence compared to cisgender women; transgender

men and women also developed breast cancer earlier than cisgender women.4 Major discrepancies in risk factors for breast cancer in

transgender patients arise from a tendency for transgender patients to avoid screening because of fear of discrimination, as well as discomfort

with a procedure that may con ict with their gender identity. Clinicians compound this health care disparity by systematically failing to screen

transgender patients.5 Interestingly, supplemented testosterone is likely a lower‐magnitude risk factor, but can either be aromatized to

estrogen or act directly on androgen receptors of nascent dysplastic cells.1 Furthermore, extrapolating from data in cisgender women,

mastectomy likely reduces (by 90%) breast cancer risk in transgender men.6

LJ was assigned a female sex at birth but has felt gender‐diverse since childhood. They use they/them pronouns, identify as gender‐nonbinary

leaning male (trans‐masculine), and have very supportive friends and family. At age 37 in 9/2004, LJ developed stage IIIC (T3N3M0)

ER+/PR+/HER2‐in ltrative ductal carcinoma (IDC) of the left breast and underwent mastectomy with axillary lymph node dissection followed by

uorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy and chest wall radiation from 10/2004 to 2/2005. While they tested negative for

BRCA mutations, in 3/2005 they underwent right simple mastectomy and TAH/BSO for both prophylactic as well as gender‐a rming purposes.

They subsequently completed adjuvant endocrine therapy from 2005 to 2010 consisting of tamoxifen, which was complicated by nausea,

prompting a switch to exemestane in mid‐2007. As neither of the mastectomies was followed by immediate reconstruction, in 11/2015 and

6/2016 they underwent bilateral chest reconstructions with fat grafting in order to correct areas of contour irregularity and to masculinize the

chest.

LJ started using subcutaneous testosterone cypionate ~80 mg every other week as part of a gender transition in 2/2017. Labs in 8/2018 were

notable for serum total testosterone 291 ng/dL (below the goal range of 400‐800 ng/dL) and serum estradiol 38.7 pg/mL (above the expected

postmenopausal range of <20 pg/mL). Given their desire to continue gender‐a rming hormone therapy, testosterone was continued at 100 mg

every other week. In 4/2019, serum testosterone increased to 816 ng/dL and estradiol remained elevated at 43.9 pg/mL. The elevated estradiol

https://onlinelibrary-wiley-com.ezproxy4.library.arizona.edu/doi/full/10.1111/tbj.13829 1/4


level was suspected by their oncologist to be secondary to the peripheral aromatization of the testosterone cypionate. In an attempt to mitigate

the risk of ongoing gender‐a rming testosterone therapy on the recurrence of their ER+ IDC, LJ was restarted on exemestane 25 mg daily. By

7/2019, serum testosterone continued to rise to 1343 ng/dL and estradiol remained stable at 42.1 pg/mL. Because the goal of testosterone

supplementation is to maintain serum levels between 400 and 800 ng/dL, with peak levels not exceeding 1000 ng/dL, the dose of LJ’s

subcutaneous testosterone was decreased to 40 mg weekly and exemestane 25 mg daily was continued. By 1/2020, serum testosterone was

670 ng/dL and estradiol was 15 pg/mL.

LJ is now 15 years from their original breast cancer diagnosis. Patients in the general population with a history of N3 IDC have approximately 2%

risk per year of developing a recurrence.7 Whether testosterone supplementation this far‐out from the original cancer diagnosis augments that

risk is unknown. Unfortunately, LJ’s original surgery was performed at an outside institution that no longer has their para n tissue block, so

whether their original tumor was androgen receptor‐positive is unknown. We plan to continue providing gender‐a rming hormone therapy to

LJ, with regular chest wall surveillance, monitoring of estradiol and testosterone levels, and an open dialogue about the risks and bene ts of

ongoing hormonal supplementation.

There are now 23 documented cases of transgender men with breast cancer, including six patients who had not received testosterone prior to

their cancer diagnosis. Five of the patients received either a selective estrogen receptor modulator (SERM) or an aromatase inhibitor (AI) as part

of their cancer treatment.1, 3 However, there are no documented cases of either of these drug classes being administered with testosterone

therapy after cancer treatment was completed in order to mitigate the risk of recurrence in a patient with a past medical history of breast

cancer (though this strategy has been previously discussed by others).8 As an irreversible AI that blocks peripheral conversation of testosterone

to estradiol, exemestane is a logical o ‐label option for reducing the risk of testosterone supplementation in a trans‐masculine patient with a

history of ER+ breast cancer. While the performance of AIs in the setting of concurrent testosterone administration in transgender men is

unknown, in cisgender men the addition of an AI to supplemented testosterone has been shown to decrease serum E2 levels that would

otherwise increase as a result of the testosterone administration.9 Moreover, AIs have been shown to be superior to tamoxifen with respect to

disease recurrence and overall survival in cisgender women with ER+ breast cancer.10 Nevertheless, more research is needed to assess the

relative risk of testosterone supplementation in trans patients with a history of ER+ IDC and to evaluate the e cacy of various formulations of

testosterone and AIs in mitigating that risk.

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