Breast Cancer Case using Tamoxifen during Pregnancy : A Case Report and Literature Review

This is a case of 32 years old nulliparous female who was diagnosed in November 2004 as a case of carcinoma of the right breast , luminal A , (Estrogen Receptor positive Progesterone receptor negative, Her 2 negative, Ki67 10 %), poorly differentiated invasive ductal cancer, TNM stage,T2 N0 MO. She had a wide local excision and axillary clearance. As she is a case of low risk early stage luminal A breast cancer; she was not given chemotherapy, instead she had a course of external irradiation and was put on Tamoxifen (Astra Zeneca, 20 mg daily), and was advised not to get pregnant during this treatment, but she got pregnant and delivered normally a healthy infant, although Tamoxifen is potentially teratogenic.


Introduction
Breast cancer is the commonest cancer among females worldwide.In Sudan it's the leading cancer in females.It forms (30-34%) of all female cancers, 40% are below the age of 45years, i.e. within the reproductive age, this reflects our population pyramid [1].
Carcinoma of the breast is the most common malignancy occurring during pregnancy [2].Tamoxifen is a non-steroidal drug which has estrogenic and an anti-estrogenic effect.It stimulates ovulation and has a teratogenic effect when used during pregnancy that has been established in animals and humans [3].Tamoxifen and come immediately for follow up.

Case Report
She remained well, until September 2011, when she was seen at an antenatal clinic, where a four months pregnancy was confirmed and was therefore referred to us.
Abdominal ultrasound showed 17weeks gestation with no abnormality, (EDD = 10 th Feb 2012), and no evidence of metastases.Clinically there was no evidence of local recurrence or metastases.Her laboratory investigations were normal.After counseling the couple, they were very keen to keep the pregnancy and accepted the consequences, as she is a nulliparous and they were married for 4 years.So the pregnancy was maintained, and she was followed with regular ultrasound of the abdomen.Amniocentesis testing was not a available, she delivered normally a healthy infant on the 15 th Feb 2012.
She was then followed regularly; she remained well with no evidence of disease when she was last seen at the follow up clinic in March 2017.

Discussion
Breast cancer is the commonest cancer in Sudanese women [1].During pregnancy Tamoxifen and its metabolites affects the rapidly growing fetal tissue.It leads to birth defects in 20% of exposures [2][3][4][5][6][7][8][9].Astra Zeneca data base records of patients exposed to Tamoxifen during pregnancy, showed 16 live births with congenital abnormalities and 122 live births without malformations.In addition there were 12 spontaneous abortions, 17 terminations of pregnancy without fetal defects, six terminations of pregnancy with fetal defects, two still births without malformations, two still births with malformation and another 57 unknown outcomes [10].
Tamoxifen induced abnormalities include Goldenhar's syndrome; ambiguous genitalia, vaginal bleeding and abortions, yet several reports described exposure to Tamoxifen with healthy neonates [5].Clark et.al studied 85 healthy women with high risk of developing breast cancer who were given Tamoxifen prophylactially.They became pregnant while on Tamoxifen, with no fetal abnormalities observed after deliveries [11].A case reported by Tewari et.al described a case of an infant borne with ambiguous genitalia, and three other case reports described four live births with congenital anomalies, no specific abnormality is identified to be associated with exposure to Tamoxifen during pregnancy [4].The relatively high frequency of congenital abnormalities means that reliable birth control during Tamoxifen treatment is essential during its use and a washout period of two months should be observed based on the known half-life of Tamoxifen.So, there is a general agreement to postpone Tamoxifen treatment until after delivery [10].There are no prospective studies assessing the effect of termination of pregnancy on survival.
Our patient got pregnant while on Tamoxifen, in spite of the fact that she and her husband were counseled, the risks were explained, and was advised not to get pregnant while on Tamoxifen and to have an intrauterine contraceptive device, but she didn't use any form of contraception as she was very keen to get pregnant due to the social pressures from the husband and the family and the fear that her husband may divorce her or remarry.But fortunately she delivered a normal infant, similar cases were reported by Isaacs et al. [7], Oksuzogolo et al. [9], and Emra Koca et al. [12].

Conclusion
Using Tamoxifen during pregnancy is contraindicated because it causes birth defects in 20% of the cases, so good counseling of Breast Cancer premenopausal women treated with Tamoxifen is important.They should be advised not to get pregnant and to stop DOI 10.18502/sjms.v12i2.921