Postpartum breast cancer represents a high-risk, under-recognized subset of young women’s breast cancer. The lack of clear identity for postpartum breast cancer is due in part to both the “dual effect” that pregnancy has on the incidence of breast cancer diagnosis, being initially promotional of and eventually protective against breast cancer. Also, pregnancy has different effects on the prognosis of breast cancer, depending on how the two events overlap, and these have added to the lack of recognition of postpartum breast cancer.
All women, regardless of their age at the time of childbirth, experience a transient increase in their risk for a breast cancer diagnosis in the ensuing decade or more of life after giving birth.[1-5] Increased maternal age correlates directly with both the peak level and the duration of this increased risk. If a woman safely navigates these postpartum years, then eventually the prior pregnancy confers reduction in the risk for postmenopausal breast cancer, especially if the woman was younger than 30 years old at the time of her first childbirth. The protective effect of childbirth on postmenopausal breast cancer is the far more commonly recognized interaction and has overshadowed the fact that premenopausal, postpartum women must safely navigate the ensuing decade(s) of life without a breast cancer diagnosis before the benefit of this risk reduction can be gained. In 2005, the National Center for Health Statistics reported that, for the first time, more US women were electing to have their first child at age 35 or older than were having their first child before 20 years of age.[6] Moreover, the US woman’s average age of first childbirth, 25 years, is actually lower than that of women in other developed countries.[7] These cultural trends suggest that the incidence of postpartum breast cancer will rise worldwide, and indeed, epidemiology reports from Sweden and Japan have documented this increase to be occurring.[8,9]
Pregnancy-associated breast cancer, the term more commonly used to report on cancers diagnosed in association with a concurrent or very recent pregnancy, needs to be recognized as two distinct subsets of disease: cases diagnosed during pregnancy and those diagnosed up to several years postpartum.[10] This distinction is important because these two subsets carry different levels of risk for recurrence and death. Large epidemiologic studies and a recent meta-analysis demonstrate that women diagnosed and treated during pregnancy face no increase in risk of death due to the concomitant pregnancy.[10-12] Conversely, women diagnosed with breast cancer 5 years or more after giving birth to their last child face up to an approximate threefold increase in risk of breast cancer metastasis and death, for reasons that remain under investigation.[11-13] This increased risk is not simply a result of altered frequencies of known clinical risk factors, such as higher stage of breast cancer at diagnosis or a higher proportion of the more aggressive biologic subtypes of breast cancer.[13] Dr. Pepper Schedin first proposed, and with her team has subsequently identified, the process of postpartum involution, in which the breast returns from lactation (or from pregnancy directly if lactation does not occur) to the resting state, as both tumor-promoting and increasing the metastatic capability of postpartum breast cancer.[5,14] Research is ongoing to identify the specific mechanisms by which postpartum breast involution worsens the prognosis of breast cancer in young mothers.
Currently in the United States, each year there are an estimated 27,000 cases of women diagnosed with breast cancer at 45 years of age or younger.[15,16] The proportion of patients in this subset, which represents about 13% of all incident US cases annually, appears to be similar in other developed countries but is reported to be much higher and associated with overall poorer breast cancer survival in countries of the Far East and Africa, and in India.[17] Conservative estimates of the frequency of postpartum breast cancer in the United States suggest that as many as 12,000 women annually will be diagnosed with this condition up to 5 years from their last childbirth,[13] representing a unique high-risk subset of breast cancer that is far more common than has been widely recognized.
My Approach to the Newly Diagnosed Patient
My approach to a woman newly diagnosed with a postpartum breast cancer starts with considering the woman first and the cancer second. With rare exceptions, women with postpartum breast cancer are in the age range in which they meet recommended criteria for undergoing genetic counseling and appropriate testing, regardless of the family history. Many postpartum breast cancer cases will be in women under age 35, and consideration of testing for mutations in p53 and possibly PTEN, or other rare genetic mutations, as well as mutations in the BRCA genes, is indicated.[18] Epidemiologic studies have suggested an interaction between the age of the mother, the presence of a family history of breast cancer or BRCA mutation, and the diagnosis of a pregnancy-associated breast cancer,[10,19-22] but further research is needed to elucidate exactly how the increased risk of breast cancer from prior childbirth and increased risk from an inherited genetic abnormality overlap.
Key Points in the Management of Postpartum Breast Cancer
- Postpartum breast cancer is a high-risk subset of young women’s breast cancer that is common and increasing in incidence worldwide
- Postpartum breast cancer is best managed using a multidisciplinary approach that incorporates upfront genetic counseling, fertility and contraceptive counseling, and a high level of patient and family support from diagnosis to survivorship.
- There is an unmet need in this setting to understand how to use targeted therapy to alter the increased risk of metastasis and death from postpartum breast cancer.
The next important considerations that I address for a young mother newly diagnosed with breast cancer are her fertility and family planning.Postpartum breast cancer interrupts a woman’s life in many ways. For example, patients can range from a nursing mother with an infant who now needs to undergo forced weaning, to a woman actively trying to conceive a subsequent child who must delay her plans, to a woman who has completed childbearing and has taken (or is considering) definitive steps to prevent future pregnancy. Therefore, in my initial evaluation I start with identification of where the individual woman’s needs fall within this spectrum and then proceed to referral for fertility preservation and/or appropriate contraceptive counseling as simultaneous considerations prior to initiation of treatment. I find it is especially important to provide information regarding the data demonstrating lack of increased risk from a subsequent pregnancy for metastatic recurrence in women previously treated for breast cancer,[23] since many young women assume that the option to conceive again is gone or is too risky due to the current breast cancer diagnosis. I tailor this information to the woman’s breast cancer stage at diagnosis, as stage IV breast cancer would be a considerable contraindication to future pregnancy, whereas earlier stages at diagnosis need not be. It is not yet known why the risk for metastasis is different if the pregnancy occurs after treatment rather than preceding the diagnosis, as in a postpartum breast cancer. Currently, options for fertility preservation have expanded and include embryo banking; egg banking; and treatment with goserelin, a luteinizing hormone–releasing hormone (LHRH) analog for “ovarian rest” during chemotherapy.[18,24] Lastly, pregnancy testing prior to diagnostic procedures involving radiation exposure or treatment initiation must also be remembered.
After individual patient considerations and concerns have been addressed, I return to discussing the cancer itself with my patient. In the Colorado Young Women’s Breast Cancer Cohort Study, stage at diagnosis and frequency of hormone receptor or human epidermal growth factor receptor 2 (HER2/neu) positivity or biologic subtype of cancer for women with postpartum breast cancer were similar to frequencies in nulliparous and later postpartum women.[13] The data set in this study is predominantly Caucasian, and the average body mass index is in the normal range, reflective of Colorado’s demographics and low rate of obesity. Therefore, it is expected that the presentation of postpartum breast cancer will vary nationally and worldwide, as the confounding risk factors for breast cancer in other populations will vary. For the moment, the mechanisms underlying the increased risk of postpartum breast cancer and how to effectively target them for improved survival remain under investigation. Therefore, at present I recommend that treatment for women diagnosed with postpartum breast cancer follow current guidelines for premenopausal breast cancer, based on the stage and biologic subtype of the cancer. I will take into consideration the increased risk associated with young age and postpartum status for cases in which interventions such as chemotherapy or radiation would be otherwise of borderline indication. Prior to initiation of any treatment, multidisciplinary input from surgery, radiation oncology, and medical oncology is crucial to ensure that the young woman understands all of her options and their potential risks and benefits. A woman’s fear of not being alive to raise her child/children is a dominant aspect of a postpartum breast cancer diagnosis that needs to be addressed to ensure the best chance for her to make clear, informed treatment choices. Key points to emphasize in discussions with the patient include (1) the potential for curative treatment; (2) the difference between risk reduction to avoid metastasis and improve survival vs approaches to reduce the risk of a subsequent primary breast cancer, to permit a wider range of surgical choices[25]; and (3) the medically safe opportunity for her to take the time to obtain second opinions and make treatment decisions. For the young mother with postpartum breast cancer, the physician’s early identification of her support system, financial state, religious or spiritual beliefs, work requirements, and childcare options are extremely important in facilitating her overall care. Early incorporation of nurse navigators, social workers, and counselors, as well as engagement of the woman’s primary care provider(s) are critical steps toward providing patient-centered multidisciplinary care. Referral to nationally recognized online sources of young women’s breast cancer–specific information, such as the websites of the Young Survival Coalition (www.youngsurvival.org) and Living Beyond Breast Cancer (www.lbbc.org), can be very beneficial and potentially help avoid the risk of misinformation obtained through Internet activity.
As stated above, until targeted therapies are identified for patients at increased risk for postpartum breast cancer, treatment planning for postpartum breast cancer should follow current guidelines for premenopausal breast cancer. As treatment is initiated, I also document baseline exercise habits, dietary patterns, and fatigue levels as three important interrelated components of all breast cancer cases that can be exacerbated in the postpartum woman due to prior recent pregnancies and young children to care for. I counsel all my patients to initiate or sustain exercise routines throughout treatment and recovery to help prevent weight gain and, potentially, treatment-related fatigue.
Whenever possible, young women with breast cancer, postpartum or otherwise, should be encouraged to participate in clinical trials appropriate to their disease setting. Clinical trials specific to young women and the risk of postpartum breast cancer are needed and can benefit from the use of focus groups and participation of young advocates to ensure feasibility and acceptability of the research approach. Lastly, all databases on breast cancer need to incorporate full parity data, not just age at first birth, to enhance the ability to study postpartum breast cancer and continue to address the long list of unknowns for this high-risk patient subset.
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
References:
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