Commentary (Brown/Armstrong): Pregnancy and Breast Cancer

Drs. Partridge and Schapira are to be complimented on a concise and comprehensive review of pregnancy before, during, and after a diagnosis of breast cancer. As women are able and willing to defer pregnancy until later in life, the issues addressed in this article will be encountered with increasing frequency in oncology. Cultural Shifts
Two parallel social and hormonal changes have taken place in this country and others over the past 150 years. The first is earlier age of menarche; the second is later age of first pregnancy. Animal studies indicate that the mammary gland is most susceptible to carcinogenic effects before the first pregnancy.[1] The period between early breast development, marked by menarche, and the terminal differentiation of mammary epithelial cells with first full-term pregnancy may be a particularly sensitive time. It is estimated that this window of vulnerability has increased approximately fourfold since the late 1800s, when reliable records were first kept. In 19th century North America, age at menarche was 16 and age at first full-term pregnancy was 19-a 3-year window. In North America today, age at menarche is 12 and age at first full-term pregnancy is 24- a 12-year window.[2,3] Women in developed countries are unlikely to return to reproductive patterns that were typical of a century ago in order to reduce their chance of developing breast cancer. However, if the mechanism(s) by which pregnancy and breast-feeding protect against breast cancer were better understood, it might be possible to mimic these effects therapeutically.[4] As the authors note, we clearly have a long way to go. Obstacles to Diagnosis and Treatment
The health-care focus for many pregnant women shifts toward the well-being of the developing fetus. This, coupled with the difficulty in detecting a tumor in the changing gravid female breast may lead to a delay in diagnosis and a more advanced stage at time of presentation.[ 5] Is this also due to a decreased emphasis on thorough clinical breast exams during prenatal visits? Breast cancer is the second most common malignancy in pregnancy, and should be in the differential diagnosis for new breast complaints or abnormal breast findings during pregnancy.[6] Whatever the primary culprit may be, awareness and communication are critical. What is also clear from this article is that a standard of care for treatment of breast cancer during pregnancy does not exist. As oncologists we strive to inform our patients about the benefits, risks, and limitations of treatment. The addition of the pregnancy and the fetus as additional complicating factors magnifies the limitations of our knowledge, especially for adjuvant therapy recommendations. The medical, social, and spiritual issues of the patient must be taken into account; however, every patient deserves to hear and understand all options. As Drs. Partridge and Schapira point out, addressing these complex issues requires a strong multidisciplinary approach involving the obstetrician, neonatologist, surgeon, radiation oncologist, pathologist, and medical oncologist. All members of the team must be involved in outlining treatments, assessing treatment toxicities and benefits, and aiding the patient as she weighs her options. Difficult Decisions
Once a diagnosis of breast cancer during pregnancy is made, the patient will be asked to make some of the most difficult decisions of her life. Should I terminate this pregnancy? Should I accept less than the recommended treatment because I am pregnant? Should I delay optimal treatment until after delivery? Should I accept the risks to the fetus of exposure to treatment during pregnancy? Most of the information we use to advise patients of these risks is meager, retrospective, and susceptible to recall bias.[7] A prospective, centralized, national registry of mothers and infants treated during pregnancy/gestation would go a long way toward addressing outcome data in this unique situation. Meanwhile, guidelines that address ethical issues in the treatment of pregnant women and the developing fetus should be reviewed before a pregnant woman is treated.[8] Finally, in addressing the issue of pregnancy after breast cancer treatment, the authors state that "[c]onventional wisdom is to wait until at least 2 years have passed from the time of diagnosis in order to get through the period of early recurrence risk." Like all recommendations, this needs to be individualized and should be based on factors we identify, our estimate of the patient's risk of recurrence and the hormone-receptor status of her tumor, as well as the priorities and realities of the patient, her desire to become pregnant, her age, and the realistic expectation of a successful pregnancy. Conclusions
This review meets its stated goals, providing an excellent review of what is known and what is unknown about the association between pregnancy and breast cancer. That said, it also highlights the unfortunate limitations in our understanding of how pregnancy affects breast cancer risk, what treatment is best for the pregnant breast cancer patient, and the safety of pregnancy after breast cancer.

Disclosures:

The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Michels KB, Willett WC: Breast cancer- early life matters. N Engl J Med 351:1679- 1681, 2004.
2. Forrest JD: Timing of reproductive life stages. Obstet Gynecol 82:105-111, 1993.
3. Mean Age of Mother, 1970-2000. NVSR vol 51, no. 1. PHS 2003-1120. Available at: www.cdc.gov/nchs/pressroom/02news/ ameriwomen.htm. Accessed April 12, 2005.
4. Hamilton AS, Mack TM: Puberty and genetic susceptibility to breast cancer in a casecontrol study in twins. N Engl J Med 348:2313- 2322, 2003.
5. ESHRE Capri Workshop Group: Hormones and breast cancer. Hum Reprod Update 10:281-293, 2004.
6. Middleton LP, Amin M, Gwyn K, et al: Breast carcinoma in pregnant women: Assessment of clinicopathologic and immunohistochemical features. Cancer 98:1055-1060, 2003.
7. Woo JC, Yu T, Hurd TC: Breast cancer in pregnancy: A literature review. Arch Surg 138:91-99 (incl discussion), 2003.
8. ACOG committee opinion: Ethical considerations in research involving women. Number 290, November 2003: Committee on Ethics. Int J Gynaecol Obstet 86:124-130, 2004.