The pregnant mother with breast cancer: Diagnostic and therapeutic management

doi:10.1016/j.ctrv.2005.04.010

Cancer Treatment Reviews

Volume 31, Issue 6, October 2005, Pages 439-447

https://doi.org/10.1016/j.ctrv.2005.04.010 Get rights and content

Summary

This review describes the epidemiology, pathology, clinical picture and therapeutic management of pregnant women with breast cancer. In addition, it covers other important issues like the safety of both diagnostic and treatment procedures, the indications for pregnancy termination, the mother and fetal outcome as well as the metastatic potential to the placenta and/or fetus. Several recommendations are also provided.

Introduction

Cancer complicates approximately 1 per 1.000 pregnancies and accounts for one-third of maternal deaths during gestation.[1], [2] The malignant tumours most commonly diagnosed in pregnancy are those with a peak incidence during the woman’s reproductive period such as breast, cervical, melanoma, thyroid cancer as well as lymphomas and leukemias. As the trend for delaying pregnancy into the later reproductive years continues, other malignancies may occur, i.e., colorectal or lung cancers.

The reproductive system is affected by malignant growth more frequently than other systems during pregnancy. Breast and cervix are the most predominant sites followed by ovarian, endometrial and vulvar carcinoma or trophoblastic tumours. Approximately 3% of women detected with cancer of the reproductive system will have a coexisting pregnancy. Diagnostic delay of those tumours is not a rare phenomenon due to masking of symptoms and signs by the normal changes associated with pregnancy.³

The management of a pregnant mother with cancer is difficult and emotionally driven and often requires the participation of the doctor, the patient and her family. The main concerns of both the obstetrician and the oncologist are to save mother’s life, to protect the fetus and to keep the woman’s reproductive system intact. The ideal combination is to cure the mother from breast cancer and to deliver a healthy baby. In addition, difficult ethical and religious issues complicate the final decision when the management of the pregnant patient with breast cancer is incompatible with continuation of the gestation.[4], [5]

Section snippets

Incidence

In 1955 White reviewed 45,881 cases of breast cancer treated between 1850 and 1950, from whom 1296 women (2.8%) had a coexistent pregnancy.⁶

There is evidence that the risk of pregnancy-associated breast cancer is age related. From the SEER Cancer Statistics data it becomes evident that women who have their first pregnancy before the age of 20 years have a 2–3 times less risk of developing breast cancer than women who have their first term pregnancy after the age of 30 years.⁷

The prevalence of

Pathology

In pregnancy the pathology profile of benign lesions is the same as in non-pregnant women. Almost 70% of them are fibroadenomas, lipomas or papillomas and the rest are lesions related to pregnancy, such as galactoceles, lactating adenomas, mastitis, or infarcts.[13], [14], [15], [16], [17]

The various histological types of breast cancer occur with similar frequencies in pregnant and non-pregnant women. In most of the reported series the predominant histological type is invasive ductal carcinoma

Clinical picture

The most common clinical presentation is a painless mass usually detected by breast self-examination. Bloody nipple discharge during pregnancy or lactation is a less common presenting symptom and should always be associated with a palpable mass. More rarely pregnant women are presented with typical clinical picture of inflammatory breast cancer. The “milk rejection sign” refers to the unexplained refusal of an infant to nurse from a carcinomatous breast.[3], [6], [9], [13], [21]

During pregnancy

Radiodiagnostic work-up

Imaging techniques used for staging breast cancer in a pregnant woman should be modified to avoid radiation exposure to the fetus.

Ionizing radiation (gamma rays, X-rays, particulate radiation) can potentially induce leukemia and solid tumours in children and adults. The radiation effect on fetal life seems to be dose dependent. Doses of less than 0.1 Gy have no effect on the fetus, whereas doses of 2.5 Gy and more than 3.0 Gy are associated with fetal malformations and abortion, respectively.

Therapeutic management

The management of breast cancer during pregnancy should follow the same criteria as their non-pregnant counterparts, should mainly be dependent on the disease stage and should be modified according to the needs of the mother and fetus.

Mother and fetal outcome

Since not adequate information is available from prospective studies, the knowledge of the effect of local or systemic treatment in pregnant mothers with breast cancer and the fetuses is mainly collected from retrospective reports.

The methods of deliveries applied vary in the largest series, although it seems that vaginal delivery is practically feasible. In some studies the gestational age at delivery was around 34–35 weeks. Delivery should be avoided during the maternal nadir, usually 2–3

The safety of chemotherapy and associated medical treatment during pregnancy

All chemotherapy drugs are capable of crossing the placenta. However, the first trimester is the most critical period, during which severe damage leads to spontaneous abortion. However, if sublethal damages happen chemotherapy may have detrimental effects on the fetus by inducing malformations, teratogenesis, mutations, carcinogenesis, organ toxicity or mental retardation. The rate of chemotherapy-associated fetal malformations is 12.7–17%, and that of low birth weight is 40%. In contrast, the

When termination of pregnancy is indicated?

In the 1950s and 1960s therapeutic abortion was a recommendation for pregnant women with breast cancer. Twenty years later it was observed that abortion does not prolong survival of patients, since pregnancy has no influence on the disease course.[21], [45]

Nowadays, a recommendation to terminate pregnancy has only room when pregnancy itself is an obstacle to drastic treatment. The main reasons to advocate therapeutic abortions are the following: (a) pregnant women requiring systemic treatment

Metastatic spread to the placenta and/or fetus

Metastatic spread of breast cancer cells to the placenta is extremely rare. Metastatic lesions to the placenta have been described in approximately 60 cases worldwide. Melanoma and hematologic malignancies are the commonest tumors that may invade placenta. Sporadic cases with fetal metastases have also been observed.

Up to 2001 nine cases of pregnant women with breast cancer with placental involvement have been reported, while no case with metastatic lesions to the fetus was found.[2], [3], [76]

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A total of 263 BRCA-carriers were included. Of these, 593 breast-ultrasonograms were performed in 263 BRCA-carriers for 292 pregnancies and 409 breast-ultrasonograms for 175 breastfeeding carriers. Of 36 breast biopsies in 292 pregnancies, 4 (PPV = 11%) had BC diagnosed (high grade invasive). Of 175 breastfeeding women, 25 biopsies were performed and 2 (PPV = 8%) were high grade invasive BC. Five of 6 BC were diagnosed in BRCA1 carriers, and 4/6 were screen detected. The rate of pregnancy-associated breast cancer was 6/292 (2.05%).
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Cancer during pregnancy: Proposal of a clinical care pathway based on a regional cohort
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Understanding the association of stem cells in fetal development and carcinogenesis during pregnancy
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Cancer during pregnancy is a rare event in the realm of obstetric statistics. Stem cells are known for their capability to renew their demographic to a variety of cell lineages. Embryonic stem cells (ESCs) originating from the blastocyst include haematopoietic stem cells (HSC) and mesenchymal stem cells (MSC). These cells play vital roles in the complex course of fetal growth and development. MSCs are found to suppress tumour growth by inhibiting PI3K/AKT pathway. Although a notable amount of literature is available about the occurrence of cancer during pregnancy, there is a lacuna about the interaction between the fetal stem cell (FSCs) and the cancer cells. A literature review revealed that the risk of ovarian cancer is reduced with an increase in fetal stem cells. After delivery, fetal microchimerism is observed to promote or suppress tumour growth under specific conditions. This review highlights the mechanism and extent of the association of FSC with the occurrence of various cancers during pregnancy. A new perspective on mother to fetus cancer transmission, which is commonly leukemia and melanoma, and the reasons for FSCs to respond differently to these cancers under various conditions have been identified by analyzing recent pieces of literature. This review also gives an idea about the existing and probable therapeutic benefits obtained from the FSCs in curbing the extent of maternal tumour metastasis. Stem cells are presently being manipulated to consistently express different chimeric antigen receptors or T cell receptors, countering tumour-associated antigens. Thus, this study highlights the therapeutic potential of the interesting crosstalk against haematological malignancies and solid tumours.
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ANTI-TUMOUR TREATMENTThe pregnant mother with breast cancer: Diagnostic and therapeutic management

Summary

Introduction

Section snippets

Incidence

Pathology

Clinical picture

Radiodiagnostic work-up

Therapeutic management

Mother and fetal outcome

The safety of chemotherapy and associated medical treatment during pregnancy

When termination of pregnancy is indicated?

Metastatic spread to the placenta and/or fetus

Am J Obstet Gynecol

Am J Obstet Gynecol

Curr Probl Cancer

Obst Gynecol Clin North Amer

Surg Clin North Am

Lancet

Surgery

Ann Oncol

Lancet Oncol

Gyn Oncology

Clin Breast Cancer

Int J Radiat Oncol Biol Phys

Cancer Treat Rev

Lancet Oncol

Am J Obstet Gynecol

Crit Rev Oncol Hematol

Blood

Clin Oncol

Eur J Obst Gynec Reprod Biol

Cancer in pregnancy – a review of the literature: parts 1 and 2

Obstet Gynecol Surv

Coexistence of pregnancy and malignancy

The Oncologist

The pregnant patient with malignant disease: maternal–fetal conflict

Cancer in pregnancy: maternal–fetal conflict

J Cancer Res Clin Oncol

Breast cancer and pregnancy

Arch Surg

Breast cancer and pregnancy: a review

J R Soc Med

Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation: analysis of case-control study in Japan

Jpn J Cancer Res

Carcinoma of the breast associated with pregnancy and lactation

Am Surg

Treatment of breast tumors associated with pregnancy and lactation

Ann Surg

Nodular breast lesions during pregnancy and lactation

Histopathology

Surgical management of breast masses in pregnant women

J Reprod Med

Spontaneous breast infarction associated with pregnancy presenting as a palpable mass

J Surg Oncol

Breast carcinoma in pregnant women. Assessment of clinicopathologic and immunohistochemical features

Cancer

Breast cancer associated with pregnancy

Obstet Gynecol

Breast cancer during pregnancy

Breast Dis

Carcinoma of the breast associated with pregnancy

Surg Gynecol Obstet

The relation of carcinoma of the breast and pregnancy in 283 patients

Surg Gynecol Obstet

Overall survival from breast cancer in women pregnant or lactating at or after diagnosis

Int J Cancer

Carcinoma of the breast associated with pregnancy

Br J Surg

ANTI-TUMOUR TREATMENT
The pregnant mother with breast cancer: Diagnostic and therapeutic management