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Breast Cancer and Pregnancy


Breast cancer is the most common diagnosed cancer during pregnancy. Pregnancy-associated breast cancer occurs from 1 in 1,000 pregnancies to 1 in 3,000 pregnancies. In the United States, about 3,500 cases of breast cancer are diagnosed in pregnant women every year. The average age of diagnosis is between 32 and 38 years. Pregnancy associated breast cancer is uncommon, but an increase in incidence is expected as more women delay childbirth. Pregnancy itself does not cause breast cancer. The incidence of breast cancer in pregnant women is the same as non-pregnant women in the general population. Patients with breast cancer during pregnancy are diagnosed at a more advanced stage of disease than non-pregnant patients with breast cancer.

Definition
Pregnancy-associated breast cancer is defined as a breast cancer diagnosed during pregnancy or within one year of delivery.

Clinical Presentation
Most pregnant women with breast cancer present with a palpable painless mass in the breast. Breast cancer can also present with thickening of the skin, redness mimicking an infection, and nipple discharge. Pregnancy do cause changes in the breast that may contribute to a delay in diagnosis. These include:

The breast nearly doubles in weight and size. Palpating a mass is more difficult when the breast becomes engorged
Irritation of the breast ducts may cause a bloody nipple discharge, which is usually a benign condition
The areola increases in size and changes in color

Physiologic changes during pregnancy modify the architecture of the breast considerably, and this may account for a significant portion of diagnostic delay. Due to the normal increase in secretion and release of ovarian placental estrogen and progestin during pregnancy, the breast enlarges, the ducts and lobules proliferate, and the breast prepares for active secretion. The breast structure changes, resulting in enlargement, firmness, and increased nodularity. The clinician examining the breast may mistake a dominant mass for the normal physiologic alterations of pregnancy.

Clinical Evaluation

All pregnant women should undergo a baseline breast clinical exam in the early stages of pregnancy. The clinician should evaluate promptly any suspicious findings before the breast undergo the normal physiologic changes of pregnancy. In many cases, the physician may mistake signs of disease for the normal physiologic changes of pregnancy. For that reason, the diagnosis and treatment of a pregnancy-associated breast cancer is often delay between 5 to 15 months from the onset of symptoms. Imaging diagnostic modalities include breast ultrasound and mammogram. Mammography is safe in this setting as long as the abdomen is covered with proper shielding to avoid radiation exposure to the fetus. A needle or core biopsy should follow to establish tissue diagnosis.

Surgical Treatment

Pregnant women with breast cancer should be treated by a multidisciplinary team of breast cancer specialists. Ultimately, the patient should be advised to have similar treatment as non pregnant patients, although the timing of various therapies may be affected by her concurrent therapy.
The surgical treatment should not be delayed because of the pregnancy. Since the risk of spontaneous abortion during surgery is low, pregnancy is not a contraindication to operative treatment.
Surgery is the mainstay of treatment and can be done at any time during the pregnancy. Mastectomy is the primary treatment of choice. The surgical option of breast conservation poses a dilemma when the woman is diagnosed in early pregnancy. Radiation therapy is an integral component in the treatment of breast cancer when breast conservation is elected. Radiation therapy poses a risk to the embryo/fetus. Breast conservation is an option as long as the diagnosis is made in the late second trimester or third trimester. Radiation therapy can be started immediately after delivery. Women who are diagnosed in the late stages of the third trimester can elect an earlier delivery. Surgery and radiation treatment can be started soon after delivery.

Adjuvant Chemotherapy

The side effects of chemotherapy treatment during pregnancy on the pregnancy itself and on the children are not well characterized. Treatment with chemotherapy during the first trimester is contraindicated . Treatment with tamoxifen and radiation therapy is also contraindicated during pregnancy. Genetic counseling to discuss the potential side effects of chemotherapy on the fetus should be entertained.
Chemotherapy is not given during the first trimester because of the risks of spontaneous abortion and fetal malformations. These complications are less likely in the second and third trimester. The fetus should be monitored closely. Approximately 50% of fetuses will have intrauterine growth restriction, lower birth weight, and preterm delivery. Chemotherapy should be stopped 3 weeks prior to delivery to avoid suppression of the immune system, which can increase the risk for sepsis and bleeding from either the mother or newborn.
For women with a large breast cancer or an inflammatory breast cancer, preoperative chemotherapy may be indicated.

Anti-HER2 Agents

HER2 plays an important role in renal development. Trastuzumab (Herceptin) crosses the placental barrier. Anti-HER2 agents are associated with an increased risk of anhydramnios (complete absence of amniotic fluid), and should be avoided during pregnancy.

Radiation Therapy

Radiation therapy is an integral part in the treatment of breast cancer if breast conservation is elected. Radiation is not recommended during pregnancy due to exposure of the fetus and risk associated such as congenital malformations, hematologic disorders, and childhood malignancies.
For women electing to undergo breast conservation radiation exposure to the developing fetus becomes a significant issue that needs to be addressed carefully. The amount of radiation scattered to the fetus depends on the distance of the fetus to the radiation field. Toward the end of pregnancy, the top of the uterus approaches the xiphoid and the fetus is exposed to higher doses of radiation therapy. It is widely accepted that any radiation to the developing fetus is not acceptable. Therefore, for women with breast cancer diagnosed in early pregnancy, breast conservation therapy should be strongly discouraged. Termination of pregnancy is an option if the woman elects to preserve her breast.
For patients with breast cancer discovered late in pregnancy it may be possible to proceed with breast conservation and delay radiation until after delivery.

Outcome

Several studies are conflicting regarding the outcome of pregnant patients with breast cancer. Some studies have shown that stage by stage, pregnant women with breast cancer have the same prognosis as non-pregnant women. Other studies have shown that circulating hormones in pregnancy have a negative effect on survival regardless of stage at diagnosis. This could be related to a rapid tumor growth due to the stimulation of the maternal hormones. An alternative explanation is that pregnancy may affect the maternal immune system in a way that encourages tumor growth.

Breastfeeding

Women who are undergoing active cancer treatment should not breastfeed. Although cancer cells do not pass to the infant through the breast milk, chemotherapy and radiation can have harmful effects on the newborn.

Pregnancy Following Breast Cancer

There is a group of women who has successfully completed treatment for breast cancer who will desire to have children. Several studies have found that pregnancy following breast cancer have no negative effect on the disease process. This has to be taken with caution and should be discussed with the breast cancer team.

In theory, pregnancy should not have effect in patients who has been cured of their disease since there is no residual tumor to be stimulated
In women whose tumors are estrogen receptor negative, the tumor cells are not responsive to hormonal stimulation. A subsequent pregnancy should not have an effect on the disease
Women with estrogen receptor-positive breast cancers who are not cured of their disease may have a detrimental effect if they have a subsequent pregnancy

A woman who has an advanced breast cancer with a poor prognosis should be advised against becoming pregnant for two reasons:

She could have residual tumor that could be stimulated by the high levels of circulating hormones seen in pregnancy
There is a possibility she may not survive long enough to raise the child

The possibility of future recurrence of breast cancer should be discussed with the patient. This may change the woman's desire to consider pregnancy. Breast cancer recurrence is more common within two years after the initial treatment. A prudent approach would be to recommend a 2-year waiting period prior to consider the idea of pregnancy. This would allow potential recurrent disease to manifest itself.


Conclusion

Pregnancy-associated breast cancer is a high-risk clinical entity and deserves a timely and comprehensive treatment. It is hard to overestimate the challenges of managing pregnant patients with breast cancer. Ultimately, the physicians should discuss with the patient and family all treatment options, potential risks and benefits of the different treatment modalities, and work as a team to make the best treatment decisions.