Pregnancy-associated or gestational breast cancer is defined as breast cancer diagnosed during pregnancy and up to a year after childbirth or during lactation. The condition has a reported occurrence of 2.4 to 7.3 per 100,000 pregnancies in population-based investigations.1

At KK Women’s and Children’s Hospital (KKH), pregnancy-associated breast cancer constitutes about seven per cent of breast cancers in women below the age of 45. This is similar to reported rates in literature,2 and the incidence is expected to rise with global trends of women delaying childbearing.

 

SYMPTOMS

A lump in the breast is the most common presenting symptom for pregnancy-associated breast cancer. Less common symptoms include skin redness, nipple retraction and nipple discharge. As these can mimic pregnancy-related breast changes or mastitis, symptoms such as a new lump in the breast should be carefully investigated to ensure that a malignancy is not missed.

 

UNIQUE CHALLENGES

Pregnancy-associated breast cancer poses unique challenges in diagnosis and treatment. This form of breast cancer typically occurs in young pregnant women who generally have a lower index of suspicion for cancer. Additionally, physiological changes during pregnancy, such as breast enlargement, engorgement and nipple discharge, can mask cancer symptoms and breast lumps are frequently thought to be due to pregnancy-related changes. There is an average diagnostic delay of two to six months, with diagnosis often made at a more advanced stage compared to non-pregnant patients.3

 

DIAGNOSTIC CONSIDERATIONS

For pregnant patients who present with suspicious symptoms such as a persistent breast lump, ultrasonography remains the diagnostic tool of choice. Breast ultrasonography involves no ionising radiation, has high sensitivity and specificity, can assess for axillary lymphadenopathy and is able to guide core needle biopsies for histological confirmation of cancer.

Mammography with abdominal shielding can be used as a safe imaging modality in pregnancy. However, it has a lower sensitivity and higher false negative rate compared to ultrasonography, due to dense breast tissue which may obscure changes.

Chest radiography with abdominal shielding and a modified bone scan with a lower dose of Tc99 have been reported to be safe in pregnancy, but are usually deferred till post-partum at KKH. Computed tomographic scans for staging should also be done post-partum.3

Magnetic resonance imaging is not recommended for use in pregnancy, as gadolinium can cross the placenta and it is difficult to differentiate hypervascularisation caused by malignancy or physiological changes in pregnancy.4

Ductal carcinomas form the majority (about 80%) of pregnancy-associated breast cancers. While their immunohistochemical features are similar to those found in young, non-pregnant patients, a higher rate of aggressive tumour features, such as oestrogen receptor negativity or HER2 positivity, has been reported. A higher rate of large tumour size and nodal metastasis in this group of patients4,5,6 has also been reported, as diagnosis of cancer is commonly delayed.

 

MANAGEMENT

Management of pregnancy-associated breast cancer must take both maternal and fetal well-being during the course of investigations and treatment into consideration. At KKH, patients are managed by a multidisciplinary team involving diagnostic imaging professionals, breast surgeons, oncologists, obstetricians and breast care nurses.

Staging of breast cancer can be carried out with ultrasonography of the hepatobiliary system. Surgery is a safe treatment option in all trimesters, and the insertion of temporary implants or tissue expanders during pregnancy can preserve the option of autologous flap reconstruction after delivery. Chemotherapy is safe after the first trimester and the risk of fetal malformations has been shown to be similar to patients who were not exposed to chemotherapy during pregnancy.

Radiation therapy and endocrine therapy with tamoxifen are contraindicated during pregnancy due to risks of teratogenicity (congenital malformations). Anti-HER2 therapy such as herceptin has been reported to be associated with oligohydramnios (reduced amniotic fluid volume), and should thus be avoided till post-partum.7,8,9

Termination of pregnancy has not been shown to confer a survival advantage; it remains a personal choice and should be discussed with each patient on a case by case basis.7

Published data on survival outcomes of pregnancy-associated breast cancer patients have been varied, with some reports indicating similar outcomes with non-pregnant patients and some indicating a poorer prognosis.10,11

 

CASE STUDY: BREAST CANCER DURING THE SECOND TRIMESTER OF PREGNANCY

Patient A, who was in her 30s, presented with a lump in her right breast during her second trimester of pregnancy. Concerned about the lump, she mentioned it during a routine consultation with her obstetrician, who immediately referred her to a breast surgeon for further examination.

An ultrasound of both breasts revealed a four-centimetre irregular mass in the superior aspect of Patient A’s right breast (Figure 1). Subsequently, Patient A underwent an ultrasound guided core needle biopsy of the mass, leading to a confirmed diagnosis of a triple negative (oestrogen receptor, progesterone receptor and HER2 negative) invasive ductal carcinoma.

 

Figure 1. Ultrasound image of Patient A’s right breast, indicating an irregular mass.

 

Taking into account that Patient A was in her second trimester of pregnancy, possible treatment options that were discussed included neoadjuvant chemotherapy or upfront surgery followed by adjuvant chemotherapy. She decided to undergo neoadjuvant chemotherapy, as she was keen to downstage the breast cancer and increase her surgical options.

Patient A was referred to a plastic surgeon for discussion of reconstructive surgical options and to a medical oncologist for discussion of chemotherapy. She was offered a referral to the reproductive medicine specialists for fertility preservation and her obstetrician was informed of the treatment plan and maintained surveillance throughout her pregnancy.

Patient A achieved good response to chemotherapy with significant decrease in the size of her tumour. She delivered a healthy baby through an elective caesarean section, and went on to have a breast conservation surgery and radiation therapy.

 

FAMILY PLANNING AFTER A BREAST CANCER DIAGNOSIS

An estimated seven per cent of fertile women go on to conceive after diagnosis of breast cancer. Diminished survival in patients who become pregnant after breast cancer treatment has not been demonstrated, but it is generally recommended that women with early breast cancer wait at least two years after treatment before attempting pregnancy.12 At KKH, patients who have not completed their families at the diagnosis of breast cancer are referred to reproductive medicine specialists for fertility preservation.

A diagnosis of breast cancer can be devastating and stressful for a young mother and her growing family, and patients often feel helpless and confused.13 At KKH, experienced breast care nurses provide guidance, support and assurance throughout the patient journey. Together with the patients’ family, friends and other breast cancer survivors, this forms a strong psychosocial support network to help these patients overcome the difficulties of cancer treatment.

 

MULTI-CENTRE COLLABORATION TO ENHANCE CARE

To advance care for women with breast cancer in pregnancy, together with Singapore General Hospital and National Cancer Centre Singapore, KKH has embarked on a review of the centres’ experience with treating gestational breast cancer. Our aim is to shed light on pregnancy-associated breast cancer in Singapore, gain deeper insight into the disease and improve care for this unique group of patients.

 

​Dr Tan Qing Ting, Consultant, KK Breast Department, KK Women's and Children's Hospital

Dr Tan Qing Ting believes that breast cancer treatment should be uniquely tailored to each individual patient for the best possible outcome. She completed an oncoplastic breast surgery fellowship at Nottingham Breast Institute, United Kingdom to help more patients achieve optimal oncological and cosmetic results.

As an adjunct instructor at Duke-NUS Medical School, Dr Tan is passionate about collaborative efforts looking into breast disease. An advocate of awareness and prevention, she has also given several public talks on breast cancer. In addition to her interest in young and pregnancy-associated breast cancer, Dr Tan has also published KKH’s experience with treating granulomatous mastitis, and is involved in a multi-centre study on the aetiology of mastitis.

Dr Veronica Siton Alcantara, Staff Registrar, KK Breast Department, KK Women's and Children's Hospital

With a medical degree in general surgery, Dr Veronica Siton Alcantara completed subspecialty training in breast surgery at KKH and currently runs the Breast Cancer Survivorship Clinic at KKH.

Dr Alcantara is part of the team at the KKH Breast Centre managing pregnancy-associated breast cancer, and has a special interest in research into pregnancy-associated breast cancer and breast cancer metastasis.
​Ms Me Me Win Htein, Clinical Research Coordinator, KK Breast Department, KK Women’s and Children’s Hospital

Ms Me Me Win Htein oversees various aspects of the KK Breast Department’s research activities, including project, database and grant management. Ms Me Me completed her MBBS degree in Myanmar and received her Master of Science in Biomedical Engineering from the Nanyang Technological University, Singapore.

 

References:

  1. Breast cancer in pregnancy: avoiding fetal harm when maternal treatment is necessary. Cordeiro et. al. Breast J 2017; 23(2):200-205
  2. Pregnancy-associated breast cancers: Do they differ from other breast cancers in young women? Genin et. al. The Breast 2012; 21(4):550-555
  3. Breast cancer in pregnancy. Amant et. al. Lancet 2012;379:570-79
  4. Breast carcinoma in pregnant women: assessment of clinicopathologic and immunohistochemical features. Middleton et. al. Cancer 2003;98(5):1055-1060
  5. Breast cancer in pregnancy: avoiding fetal harm when maternal treatment is necessary. Cordeiro et. al. Breast J 2017; 23(2):200-205
  6. Breast carcinoma during pregnancy. International recommendations from an expert meeting. Loibl et. al. Cancer 2006;106(2):237-246
  7. Breast cancer during pregnancy : maternal and fetal outcome. Cardonick et. al. Cancer J 2010;16:76-82
  8. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Hahn et. al. Cancer 2006;107:1219-1226
  9. Breast cancer diagnosed during pregnancy: adapting recent advances in breast cancer care for pregnant patients. Loibl et. al. JAMA Oncol 2015;1(8):1145-1153
  10. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: a case-control study of 87 cases. Genin et. al. The Breast 2016;30:222-227
  11. Prognosis of pregnancy-associated breast cancer: A meta-analysis of 30 studies. Azim Jr et. al. 2012; 38(7): 834-842
  12. Effect of pregnancy on overall survival after diagnosis of early-stage breast cancer. Gelber et. al. J Clin Oncol 2001;19:1671-1675
  13. Health care experiences among women diagnosed with gestational breast cancer. Hammarberg et. al. Eur J Cancer Care 2018;27:e12682