In the article that accompanies this editorial, Amant et al report on the prognosis of breast cancer for 311 women diagnosed and treated during pregnancy. Their experience serves to increase awareness of clinicians who may be faced with this clinical dilemma, and it reminds us of the intimate relationship between hormones and breast cancer, as well as the limited availability of firm guidance about best practices for the patient and the fetus. Breast cancer and the concomitant diagnosis of pregnancy is an unusual clinical circumstance. Many oncologists and obstetricians may not have experience or only limited exposure to cancers diagnosed during pregnancy. Even fewer may have a background for providing guidance for diagnosis and treatment in this setting. The patient in this situation is likely to be fearful not only of the existential threat to themselves, the threat to their person, and the view of death that cancer may represent but also the potential threat to their unborn fetus. The pregnancy also may be perceived as a threat to the patient’s well-being and cancer treatment may be perceived as a threat to the well-being, even survival, of the fetus. Ethical and moral constructs contribute to the concerns of the patient, family, and treatment team. A relationship between hormones and breast cancer has long been recognized. The approach put forward by Beatson to surgical intervention for breast cancer with oophorectomy demonstrated this relationship in the 1890s. Epidemiologic data regarding risks for developing breast cancer are consistent with hormonal milieu as a contributing factor for breast cancer occurrence with estrogen the main factor of risk. These observations developed into strategies for the treatment of breast cancer with ablative endocrine therapies, oophorectomy, adrenalectomy, and hypophysectomy. Clinical reports of breast cancer during pregnancy in the early twentieth century noted such a poor prognosis for these patients that treatment was deemed futile. As knowledge of estrogen receptors and their clinical role in breast cancer developed, there was persistent belief that breast cancer accompanied by pregnancy portended a poor patient survival. The concept of therapeutic abortion was a response to the belief that it was the hormonal milieu of pregnancy that resulted in poor outcomes. It was thought that if the hormonal milieu of pregnancy could be ablated, the prognosis for breast cancer might improve. Recent reports analyzing clinical outcomes for these patients have been studies of limited numbers of patients, case reports, casecontrol, and population-based matched control survival analyses, observational studies, and meta-analysis. Some have reported poor patient prognoses, whereas others have been more optimistic. Outcomes have varied, seemingly on the basis of patient and disease characteristics at diagnosis. Breast cancer during pregnancy has been characterized by more advanced disease stage, poorly differentiated tumors that are often estrogen receptor–negative, and delays in diagnosis on the part of patient and physician, assuming breast changes are benign and related to the pregnancy. Most of these reports have been retrospective in nature and have not included sufficient detail about patient and tumor characteristics to determine how generalizable the results are for routine clinical practice. Amant et al gathered a larger information base derived from multinational cancer registries and cooperative collections of retrospectively and prospectively collected data in which pregnancy was a data dictionary component. They report a substantial effort of clinical work, which helps to inform our decisions regarding care for the pregnant patient with breast cancer. Their report includes data analysis regarding prognosis for women diagnosed and treated for breast cancer during pregnancy. Pregnancy-associated breast cancer, which includes postpartum diagnosis and diagnosis of breast cancer within 1 year of delivery, was specifically excluded. Outcome measures such as disease-free and overall survival were compared between the pregnant population and matched controls retrieved from the same database. Careful measures were used to control for bias in the data analyses. In addition to including disease and patient characteristics, systemic and local therapies and types of treatment were part of the analyses. Cancer treatment was at the discretion of the attending physicians and surgeons, although guidelines were available for use. Surgery included mastectomy and breast-conserving procedures. Analyses accounted for differences in the age of the patients and controls and included analyses of regional differences in care as well as the number of patients contributed by each referring site. Thus, it is expected that these results would be generalizable to a typical scenario that might be encountered in practice. The important primary message was that there were no observed differences in disease-free or overall survival on the basis of pregnancy JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 20 JULY 1
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