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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 38-40

Pregnancy-associated breast cancer after fertility treatment


Department of Obstetrics and Gynaecology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India

Date of Submission17-Sep-2020
Date of Acceptance03-May-2021
Date of Web Publication17-Dec-2021

Correspondence Address:
Prof. Papa Dasari
Department of Obstetrics and Gynaecology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Dhanvantri Nagar 605006, Puducherry.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tofj.tofj_6_20

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  Abstract 

The incidence of pregnancy-associated cancer is on the rise. A 36-year-old lady married for three years underwent IVF for mild male factor infertility following the failure of conception with six cycles of ovulation induction and three cycles of IUI. She conceived spontaneously two months after the frozen embryo transfer cycle. She was diagnosed to have breast cancer at 32 weeks of pregnancy. Her records did not show findings of breast examination during the antenatal visits. She was advised to take chemotherapy, but she refused because of the fear of effects on the fetus and underwent LSCS at 35 weeks. An alive female baby with a weight of 2.5 kg was born. Postoperatively, she was managed with neoadjuvant chemotherapy and was referred for mastectomy. Counseling for chemotherapy should involve treating obstetrician in addition to the oncologists.

Keywords: Carcinoma breast, chemotherapy, fertility treatment, pregnancy


How to cite this article:
Dasari P, Anantharaju A, Jha N. Pregnancy-associated breast cancer after fertility treatment. Onco Fertil J 2021;4:38-40

How to cite this URL:
Dasari P, Anantharaju A, Jha N. Pregnancy-associated breast cancer after fertility treatment. Onco Fertil J [serial online] 2021 [cited 2022 Dec 9];4:38-40. Available from: https://www.tofjonline.org/text.asp?2021/4/1/38/332643




  Introduction Top


Breast cancer is the second most common cancer during pregnancy, and its incidence is on the rise and is reported to be 1 in 3000.[1] Among the reasons cited for its increased incidence are advanced age at pregnancy, genetic predisposition, and various fertility treatment techniques. The survival rates are less with pregnancy-associated breast cancer when compared to non-pregnancy–associated breast cancers.[2] This report adds to the literature on the association of fertility treatment with breast cancer and fears of a pregnant woman with breast cancer and the pregnancy outcome.


  Case Top


A 36-year-old infertile woman married for three years attended our infertility services in August 2018. She attained menarche at 16 years of age, and her cycles were regular, occurring once in 30 days lasting for three days. Her treatment history included initial six cycles of ovulation induction with oral ovulogens, after which she underwent hysterolaproscopy two years ago. Subsequently, she underwent three cycles of IUI. There was no family history of malignancies.

On examination, there was no pallor; her breasts and thyroid were normal. Systemic examination and abdominal examination were normal. Per vaginal examination, the uterus was anteverted and normal size; fornices were free. The semen analysis report was oligoasthenoteratospermia. She was advised to undergo IntraCytoplasmic Sperm Injection (ICSI), but she was lost to follow-up and underwent ICSI elsewhere in October 2018. She underwent frozen embryo transfer (FET) in November 2018 in which three embryos were transferred, and implantation did not occur.

She spontaneously conceived in January 2019 (two months after the FET cycle). Her last menstrual period was January 28, 2019. She confirmed pregnancy at five weeks by ultrasound and had regular antenatal care elsewhere and came to us for antenatal care in June 2019 at 21 weeks of pregnancy. Her anomaly scan was normal. At 24 +2 weeks of gestational age, ultrasound biometry was corresponding to gestational age. There were no gross congenital malformations. Placenta was posterior and upper segment.

There was no record of findings of breast examination during the time of antenatal visits. At 30 weeks of pregnancy, she complained of a right breast lump of two months of duration, and on examination, she had 5 × 5 cm hard mass. Malignancy was suspected, and surgery opinion was taken. Sono mammogram revealed 3.3 × 2.1 cm relatively heterogeneous hypoechoic lesion at the right breast 2 cm from neoadjuvant chemotherapy internal vascularity present, and there were no calcifications. There was another hypoechoic lesion at 7’o clock position measuring 7 × 10 mm with internal vascularity few axillary lymph nodes of 6 mm BIRADS 4A. Fine needle aspiration cytology showed ductal infiltrative adenocarcinoma. She underwent trucut biopsy on September 6, 2019, and this showed invasive ductal carcinoma: grade 1, score 5, no special type. She was advised neoadjuvant chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC) in a multidisciplinary tumor board. But she refused during counseling because of the fear of harm to the baby.

Her investigations are as follows: her complete hemogram showed Hb of 11.9 g%; total leucocyte count of 13,140/mL; N of 75%; E of 1.9%; B of 0.2%; M of 6.4%; platelets of 2,30,000 mm3; thyroid stimulating hormone of 2.33 mIU/L; 75 g GTT: 86/149/102 mg%; blood group: A Rh positive; HIV: nonreactive; HbS Ag: nonreactive; VDRL: nonreactive; liver function tests: total bilirubin: 0.23 mg/dL; direct bilirubin: 0.03 mg/dL; total protein/albumin: 6.9/3.7 g/dL; AST/ALT: 19/15 IU/L; renal function tests: urea/creatinine: 15/0.59 mg/dL; serum electrolytes: Na/K: 138/3.95 mEq/L; ECG and ECHO: normal findings.

Her fetal growth was normal, and she was hospitalized at 32 weeks. Non-stress test was reactive with a baseline of 140 bpm, variability of 10–15 bpm, with accelerations. She was counseled again for chemotherapy, but her fear persisted as her aim was to get a healthy baby. Elective LSCS was done at 35 +3 weeks of gestation on October 3, 2019 after giving antenatal corticosteroids. An alive preterm female baby was born with a birth weight of 2.53 kg, which was transferred to neonatal intensive care unit for respiratory distress. The neonate received surfactant and was evaluated and transferred to mother side after five days.

Post-LSCS, she underwent contrast enhanced computed tomography thorax and abdomen on October 12, 2019, and the report is as follows: heterogeneously enhancing lobulated mass lesion measuring 6.6 × 6.1 cm seen in the subareolar region of the right breast involving the skin surface. There is no invasion of pectoralis muscle seen. Enlarged right axillary nodes were noted, the largest measuring 2.5 × 1.3 cm, and enlarged intramammary nodes were also noted, the largest measuring 0.7 × 0.7 cm. No infraclavicular or supraclavicular nodes were seen. A solitary nodule measuring 0.5 × 0.4 cm was seen in the anterior segment superior lobe of the right lung. There was no pleural effusion. Liver, kidney, pancreas, spleen, both kidneys, and bladder were normal.

Medical oncologist advised for seven cycles of FEC (5-fluorouracil 500 mg/m2 bolus: 820 mg, epirubicin 100 mg/m2 slow IV: 165 mg, cyclophosphamide 500 mg/m2: 820 mg) regimen. The first cycle of chemotherapy was given on October 14, 2019 and the second cycle was given on November 5, 2019. She was referred to the Department of Surgery for mastectomy.


  Discussion Top


Pregnancy-associated breast cancer usually presents in the advanced stage, and diagnosis is difficult. Case series of women with breast cancer during pregnancy encountered between 1985 and 1999 reported poor maternal survival and fetal deaths during chemotherapy.[3] But a recent review highlighted that the prognosis of pregnant women with breast cancer was almost similar to the counterparts of nonpregnant women of similar age. Delaying treatment because of misconceptions will worsen the prognosis, and similar regimens used for nonpregnant women can be employed for pregnant women without adverse effects on the fetus neonate.[4]

A large cohort of 140 women with breast cancer reported the mean maternal age to be 34.8 ± 4.2 years and mean gestational age to be 13.2 ± 8.1 weeks at diagnosis. One hundred and four women received chemotherapy at a mean gestational age of 20.4 ± 5.4 weeks. The malformation rate of exposed neonates was not greater than the general population. The maternal survival rates were 100% for stage I, 86% for stage II and III disease, and none for stage IV.[5] Children of women who received chemotherapy employing FAC protocol during the second and third trimesters were followed up beyond infancy. They found no short-term complications but suggested long-term evaluation for IQ.[6] An interval of three weeks after chemotherapy is recommended prior to delivery.


  Risk factors for the development of breast cancer during pregnancy Top


It is recognized for a long time that nulliparous women and women having their first child after 30 years of age are at an increased risk of developing breast cancer, apart from early menarche and late menopause.[7] Long-time exposure to the hormones, especially estrogens, is the risk factor. Infertility is also quoted as a risk factor for the same reasons, but a study involving 12,193 infertile women (1965–1988) who received treatment with clomiphene citrate or gonadotropins for IVF and had a long-term follow-up (till 2010) did not show an increased risk.[8] The Two Sister Study that estimated the risk between pregnant women of 10 weeks and nonpregnant women after ovulation induction concluded an increased risk for those who became pregnant.[9] A recent review regarding the risk of cancer after undergoing IVF concluded that there is no evidence of an increased risk.[10] But few studies have reported an increased risk of breast cancer in women who underwent IVF after 10 years of follow-up.[11] When the risk calculation is adjusted with age at the first delivery, the risk was found to increase, but the hazard ratio did not increase for women requiring IVF at age 40 or older.[12]


  Difficulties in diagnosis of breast cancer during pregnancy Top


The size of the breast usually increases two times during pregnancy, and firmness and density also increase. These changes make clinical examination difficult and also the mammographic appearance and interpretation difficult. Further, the malignant mass lesion is painless to start with; hence, women do not have symptoms till the advanced stage. By the time breast cancer was diagnosed during pregnancy, already metastasis would have occurred, and they have large tumors with node positivity and vascular invasion.[13] A study from Nigeria reported 75% in stage IV and 25% in stage III at the time of diagnosis.[14] Pathological diagnosis is also difficult sometimes because of rapidly dividing cells during pregnancy and lactation mimicking malignant cells.[15]


  Conclusion Top


This case report shows the importance of breast examination during antenatal care, and there are conflicting reports in the literature regarding the fertility treatment and the risk of breast cancer; however, it is clear that remote from term one has to counsel the women with breast cancer to undergo neoadjuvant chemotherapy, and every effort should be made to remove the fear of the side effects of chemotherapeutic drugs on the baby. Counseling for chemotherapy should involve treating obstetrician in addition to the oncologists to allay the fear.

Acknowledgement

The authors thank the Department of Pathology, Medical Oncology and Department of Surgery.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Navrozoglou I, Vrekoussis T, Kontostolis E, Dousias V, Zervoudis S, Stathopoulos EN, et al. Breast cancer during pregnancy: A mini-review. Eur J Surg Oncol 2008;34:837-43.  Back to cited text no. 1
    
2.
Rodriguez AO, Chew H, Cress R, Xing G, McElvy S, Danielsen B, et al. Evidence of poorer survival in pregnancy-associated breast cancer. Obstet Gynecol 2008;112:71-8.  Back to cited text no. 2
    
3.
Healy C, Dijkstra B, Kelly L, McDermott EW, Hill AD, O’Higgins N. Pregnancy-associated breast cancer. Ir Med J 2002;95:51-2, 54.  Back to cited text no. 3
    
4.
Rojas KE, Bilbro N, Manasseh D-M, Borgan PI. A review of pregnancy associated breast cancer: Diagnosis, local and systemic treatment and prognosis. J Women’s Health (Larchmt) 2019;28:778-84.  Back to cited text no. 4
    
5.
Cardonick E, Dougherty R, Grana G, Gilmandyar D, Ghaffar S, Usmani A. Breast cancer during pregnancy: Maternal and fetal outcomes. Cancer J 2010;16:76-82.  Back to cited text no. 5
    
6.
Hahn KM, Johnson PH, Gordon N, Kuerer H, Middleton L, Ramirez M, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer 2006;107:1219-26.  Back to cited text no. 6
    
7.
Newcomb PA, Trentham-Dietz A, Hampton JM, Egan KM, Titus-Ernstoff L, Warren Andersen S, et al. Late age at first full term birth is strongly associated with lobular breast cancer. Cancer 2011;117:1946-56.  Back to cited text no. 7
    
8.
Brinton LA, Scoccia B, Moghissi KS, Westhoff CL, Niwa S, Ruggieri D, et al. Long-term relationship of ovulation-stimulating drugs to breast cancer risk. Cancer Epidemiol Biomarkers Prev 2014;23:584-93.  Back to cited text no. 8
    
9.
Fei C, Deroo LA, Sandler DP, Weinberg CR. Fertility drugs and young-onset breast cancer: Results from the Two Sister Study. J Natl Cancer Inst 2012;104:1021-7.  Back to cited text no. 9
    
10.
Momenimovahed Z, Taheri S, Tiznobaik A, Salehiniya H. Do the fertility drugs increase the risk of cancer? A review study. Front Endocrinol (Lausanne) 2019;10:313.  Back to cited text no. 10
    
11.
Reigstad MM, Larsen IK, Myklebust TÅ, Robsahm TE, Oldereid NB, Omland AK, et al. Risk of breast cancer following fertility treatment–A registry based cohort study of parous women in Norway. Int J Cancer 2015;136:1140-8.  Back to cited text no. 11
    
12.
Stewart LM, Holman CD, Hart R, Bulsara MK, Preen DB, Finn JC. In vitro fertilization and breast cancer: Is there cause for concern? Fertil Steril 2012;98:334-40.  Back to cited text no. 12
    
13.
Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Burke B, Sutcliffe SB, et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 1992;166:781-7.  Back to cited text no. 13
    
14.
Olatoke SA, Agodirin SO, Adenuga AT. Pregnancy associated breast cancer: An institutional experience. J Med Trop 2018;20:104-10.  Back to cited text no. 14
  [Full text]  
15.
Novotny DB, Maygarden SJ, Shermer RW, Frable WJ. Fine needle aspiration of benign and malignant breast masses associated with pregnancy. Acta Cytol 1991;35:676-86.  Back to cited text no. 15
    




 

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