Kembra L. Howdeshell1 and Michael D. Shelby1
(1)
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
Kembra L. Howdeshell
Email: howdeshellkl@niehs.nih.gov
Keywords
CancerPregnancyIncidencePrognosisBreastCervixOvaryLymphomaLeukemiaMelanoma
Introduction
Cancer diagnosed during pregnancy is rare, and the incidence rate of pregnancy-associated cancer is expected to increase as women continue to delay childbearing to their later reproductive years [38]. The definition of pregnancy-associated cancer varies from study to study, but most frequently is defined as a diagnosis during pregnancy or up to 1 year after delivery. The incidence rate of cancer diagnosed during pregnancy is reported to range from 17 to 38 cases/100,000 births [14, 21, 29, 49], while the incidence of rate of cancer diagnosed during pregnancy or up to 1 year after delivery (94–137/100,000 births) approaches the rates observed in all women of reproductive age (15–44 years old; Table 1.1) [47]. Significant increases in incidence rates of pregnancy-associated cancer over time have been reported in studies spanning the years 1977–2008; however, the tendency to delay pregnancy was only partially responsible for the increased incidence rates [14, 29]. Other factors contributing to the increase in rate of pregnancy-associated cancer over time may be improvements in diagnostic techniques and detection and increased interaction with medical services during pregnancy. It has also been hypothesized that the hormones and growth factors necessary for fetal growth may accelerate tumor growth.
Table 1.1
Incidence of malignant cancer among all women of reproductive age (15–44 years) in the USA, reported in the year 2012
|
Cancer type |
All cancer sites |
Breast |
Cervix |
Leukemia |
Hodgkin lymphoma |
Non-Hodgkin lymphoma |
Ovary |
Melanoma |
|
Incidence |
130.4a |
41.6 |
6.9 |
3.3 |
3.5 |
4.5 |
4.0 |
11.9 |
The site-specific cancers included in this table represent seven of the most frequently diagnosed cancers in women during pregnancy
aData are age-adjusted and are rates per 100,000 women as reported by Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute [47]
This chapter reviews current information regarding the incidence and prognosis of seven of the cancer types frequently diagnosed during pregnancy: breast cancer, cervical cancer, ovarian cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, leukemia, and melanoma (Fig. 1.1). These seven cancers are also among the cancers most frequently diagnosed in women of reproductive age, accounting for about 58 % of all cancers in this age group (Table 1.1) [47]. The incidence data reviewed in this chapter focus on population-based studies, while the prognosis literature focus on studies reporting matched controls and larger sample sizes as well as meta-analyses, when available. Several smaller studies that assess the incidence and prognosis of pregnancy-associated cancer are included in the National Toxicology Program monograph on Developmental Effects and Pregnancy Outcomes Associated with Cancer Chemotherapy Use During Pregnancy [42] and other reviews. The majority of studies evaluating the prognosis define pregnancy-associated cancer as a diagnosis of cancer during pregnancy or up to 1 year postpartum, which makes it difficult to determine the prognosis of patient with cancer diagnosed during pregnancy only. When data are available, this chapter also reviews the prognosis of women diagnosed with cancer specifically during pregnancy (referred to as diagnosed during pregnancy).
Fig. 1.1
Percentage of cancer types diagnosed during pregnancy in Norway from 1967 to 2002 as reported in Stensheim et al. [51] (n = 516 cases). Other types of cancers frequently diagnosed during pregnancy include the thyroid, colorectal, and brain/central nervous system [14, 21, 29, 49, 51]
Breast Cancer and Pregnancy
Occurrence Rate During Pregnancy
The incidence rate of pregnancy-associated breast cancer was reported in seven population-based studies [1, 5, 14, 21, 23, 29, 49] (Table 1.2). The crude incidence rate of breast cancer diagnosed during pregnancy was 1.3–7.9/100,000 births. The incidence rate of pregnancy-associated breast cancer increased over the time period covered by the four studies (1963–2008), which was partially attributable to a delay in childbearing to an older age [1, 5, 14, 29].
Table 1.2
Incidence of cancer during pregnancy from population-based studies
|
Crude incidence per 100,000 births (number of births) |
|||||||||
|
Reference |
Years of data |
Total number of births |
Breast |
Cervix |
Leukemia |
Hodgkin lymphoma |
Non-Hodgkin lymphoma |
Ovary |
Melanoma |
|
Haas [21] |
1970–1979 |
2,103,112 |
1.3 (28) |
10.9 (229) |
0.4 (8) |
0.7 (15) |
0.2 (4) |
0.9 (19) |
0.6 (12) |
|
Dgani et al. [12] |
1960–1984 |
1,083,652 |
–a |
– |
– |
– |
– |
2.1 (23) |
– |
|
Smith et al. [49] |
1991–1999 |
4,846,505 |
5.1 (246) |
3.6 (175) |
1.4 (67) |
2.2 (107) |
0.7 (33) |
2.4 (115) |
3.1 (12) |
|
Ives et al. [23] |
1982–2000 |
NRb |
7.9 (NR)c,d |
– |
– |
– |
– |
– |
– |
|
Andersson et al. [5] |
1963–2002 |
4,156,190 |
2.4 (99) |
– |
– |
– |
– |
– |
– |
|
Abenhaim et al. [1] |
1999–2008 |
8,826,137 |
6.5 (573) |
– |
– |
– |
– |
– |
– |
|
Lee et al. [29] |
1994–2008 |
1,309,501 |
7.3 (95) |
1.8 (24) |
– |
– |
– |
1.5 (19) |
– |
|
Al-Halal et al. [2] |
1999–2008 |
8,826,137 |
– |
3.3 (294) |
– |
– |
– |
– |
– |
|
Eibye et al. [14] |
1977–2006 |
2,427,670c |
3.7 (91)c |
4.0 (96)c |
– |
– |
– |
– |
5.8 (141)c |
|
Bannister-Tyrrell et al. [7]e |
1994–2008 |
1,309,501 |
– |
– |
– |
– |
– |
– |
14.9 (195) |
|
El-Messidi et al. [15] |
2003–2011 |
7,916,388 |
– |
– |
– |
8.1 (638) |
– |
– |
– |
|
El-Messidi et al. [16] |
2003–2011 |
7,917,453 |
– |
– |
– |
– |
5.4 (427) |
– |
– |
aNo data reported for specific cancer type
bNot reported
cTotal number of pregnancies, including live births and induced abortions; incidence rates based on pregnancies
dIncidence rate of cancer diagnosed during pregnancy only was estimated as one-third of the incidence of cancer diagnosed during pregnancy and up to 1 year postpartum
eFollow-up study of same population reported in Lee et al. [29]
Impact of Pregnancy on Prognosis
Pregnancy and lactation increase the size and density of the breasts, making it more difficult for the patient or the clinician to detect masses in the breasts. This is thought to lead to a delay in diagnosis of some tumors and, hence, to the presence of more advanced-stage tumors at diagnosis in many pregnant breast cancer patients when compared to their nonpregnant counterparts [6, 44]. Petrek and Seltzer [44] reviewed the evidence for pregnancy impacting the prognosis of breast cancer. They reported that women with pregnancy-associated breast cancer are more likely than nonpregnant patients to have positive lymph nodes and less likely to have tumors smaller than 2 cm. They noted that pregnant women had a 2.5-fold higher risk of diagnosis with metastatic breast cancer and a significantly decreased chance of an earlier stage (stage I) diagnosis. These observations are supported by two recent studies reporting that pregnancy-associated breast cancer cases have more advanced disease [24, 52] and larger tumors at diagnosis than nonpregnant breast cancer patients [52].
A majority of studies report that survival is worse in pregnancy-associated breast cancer patients than in their nonpregnant counterparts. In a meta-analysis of 30 retrospective control-matched, population-based, and hospital-based studies published from years 1969 to 2012, Azim et al. [6] observed that pregnancy-associated breast cancer was associated with poor prognosis, even after adjustment for confounding factors (e.g., age, stage of tumor). However, both univariate and multivariate analyses observed significant heterogeneity among the studies assessing the overall survival of pregnancy-associated breast cancer. The authors suggest that part of the poor prognosis may be due to delayed diagnosis and suboptimal systemic therapy [6]. Several recent publications of control-matched studies have reported similar results of shorter disease-free survival and lower overall survival of pregnancy-associated breast cancer cases compared to a nonpregnant breast cancer cohort [3, 13, 24, 36, 46]. However, limitations of these studies include a lack of adjustment for chemotherapy regime or incomplete data on chemotherapy treatment to do so reliably and a lack of data on time between diagnosis and treatment. Another recent study did not observe a difference in overall survival between these two patient groups [52].
The prognosis of breast cancer diagnosed during pregnancy appears to be largely comparable to the nonpregnant cohort. The meta-analysis of 30 studies by Azim et al. [6] reported a slightly greater risk of death for breast cancer patients diagnosed during pregnancy only compared to nonpregnant controls; however, the pooled hazard ratio of the multivariate analysis was not statistically significant (pooled HR: 1.29; 95 % CI [0.74–2.24]) and had high heterogeneity. Six studies published since the meta-analysis report comparable overall survival rates between breast cancer patients diagnosed during pregnancy and a nonpregnant breast cohort [4, 13, 17, 34, 36, 52]. In particular, two studies controlled or adjusted for systemic treatment in their analysis and observed comparable clinical outcomes for breast cancer patients diagnosed during pregnancy and nonpregnant breast cancer patients [4, 34]. Litton et al. [34] conducted a matched case-control study of breast cancer patients treated during the second and third trimesters with standard 5-fluorouracil-adriamycin-cyclophosphamide (FAC) therapy matched on age and stage of cancer with a nonpregnant cohort. The authors reported comparable, if not improved, disease-free survival, progression-free survival, and overall survival of the breast cancer patients treated during pregnancy compared to the nonpregnant patients [34]. Amant et al. [4] conducted a cohort study using data from an international registry of women diagnosed with breast cancer during pregnancy compared to nonpregnant breast cancer patients and adjusted for age, stage, grade, hormone receptor status, histology, human epidermal growth factor 2 status, type of chemotherapy (administered in the second or third trimester), and any postpartum treatment with trastuzumab, radiotherapy, and hormone therapy. The authors observed similar disease-free and overall survival of women diagnosed with breast cancer during pregnancy compared to the nonpregnant cohort [4].
Cervical Cancer and Pregnancy
Occurrence Rate During Pregnancy
Cervical cancer was among the three cancers most frequently diagnosed during pregnancy in four of the five population-based studies reviewed herein [2, 14, 21, 29, 49] (Table 1.2). The crude incidence rate of cervical cancer diagnosed during pregnancy was 1.8–10.9 cases/100,000 births. Haas [21] reported that the age-adjusted incidence rate of cervical cancer diagnosed during pregnancy increased with increasing maternal age, which she suggests may be due to the introduction of cervical screening programs during the time period of the study (1970–1979). However, the age-adjusted rate of cervical cancer did not appear to rise over time in two other population-based studies that were conducted at either a later date (1999–2008) [2] or over a broader time period (1977–2006) [14]. Cervical intraepithelial neoplasia, a precursor to cervical cancer, appeared to increase over time and was observed in younger patients (<25–34 years), whereas cervical cancer patients were older (25 to ≥35 years) [2].
Impact of Pregnancy on Prognosis
There is general agreement in the literature that pregnancy does not appear to change the prognosis of cervical cancer. In their review of the literature, Germann et al. [19] stated that the majority of the studies do not report a difference in the prognosis of pregnancy-associated invasive cervical cancer. No differences in survival between pregnancy-associated cervical cancer cases and nonpregnant patients with cervical cancer have been reported by at least three retrospective cohort studies published since 2005 [28, 45, 51], including one study that also evaluated the cause-specific survival by timing of diagnosis (during pregnancy or during lactation) and found no significant differences with nonpregnant cervical cancer patients [51].
Some studies reported unique characteristics of pregnancy-associated cervical cancer. A younger age at diagnosis was reported for women diagnosed with pregnancy-associated cervical cancer versus nonpregnant patients [37, 40]. Women with pregnancy-associated cervical cancer were more likely to be diagnosed at stage I than nonpregnant patients [19, 37]. Lee et al. [28] reported that, unlike nonpregnant cervical cancer patients, the depth of the stromal invasion did not correlate with the involvement of the lymph vascular space or lymph node metastasis in women diagnosed with pregnancy-associated cervical cancer. The authors suggest that pregnancy-induced enlargement of the uterine cervix may reduce the depth of the stromal invasion, which may lead to earlier lymph node metastasis [28].
Lymphomas and Leukemia and Pregnancy
Occurrence Rate During Pregnancy
Five population-based studies that addressed the occurrence rate of pregnancy-associated lymphohematopoietic cancer are reviewed [15, 16, 21, 29, 49] (Table 1.2). Of the three lymphohematopoietic cancer types, Hodgkin lymphoma was the most commonly diagnosed during pregnancy. The crude incidence rate of Hodgkin lymphoma diagnosed during pregnancy ranged from 0.7 to 8.1/100,000 births across the three available studies [15, 21, 49]. The incidence rate of Hodgkin lymphoma appeared to be relatively stable in the USA from 2003 to 2011 when assessing the age-adjusted incidence rates [15], although the rates were greater than those observed in the USA in the 1990s [49] (Table 1.2). Leukemia was the second most common lymphohematopoietic cancer occurring in pregnancy with crude incidence rates for diagnosis during pregnancy of 0.4–1.4/100,000 births [21, 49]. There were no data reported regarding the incidence rate of leukemia over time. Finally, the crude incidence rate of non-Hodgkin lymphoma diagnosed during pregnancy was 0.2–5.4/100,000 births [16, 21, 49]. The crude incidence rate of non-Hodgkin lymphoma diagnosed during pregnancy was observed to increase significantly from 4.4/100,000 birth in 2003 to 7.7/100,000 births in 2011 in a study conducted in the USA [16]. One study reported the cases of pregnancy-associated lymphoma or leukemia as a combined incidence rate of 4/100,000 births diagnosed during pregnancy from 1994 to 2008 [29], which was similar to the rates of the three cancer types combined from Smith et al. [49].
Impact of Pregnancy on Prognosis
The impact of pregnancy on the prognosis of Hodgkin lymphoma and leukemia appears negligible, while there are limited data available on the prognosis of non-Hodgkin lymphoma so the impact is unclear. However, these conclusions are based primarily on small retrospective series and case reports (see below). The only retrospective, population-based cohort study to evaluate prognosis of the pregnancy-associated lymphohematopoietic cancers (combined) found no difference in the rates of cause-specific death between women diagnosed during pregnancy and nonpregnant cases [51]. The authors did not evaluate the prognosis of Hodgkin lymphoma, non-Hodgkin lymphoma, and leukemia separately.
Hodgkin Lymphoma
Two cohort studies reported no differences in prognosis for pregnancy-associated Hodgkin lymphoma compared to nonpregnant patients. In a retrospective cohort study from one hospital, Barry et al. [8] reported no difference in survival curves or median survival times between 84 pregnancy-associated Hodgkin lymphoma patients and 228 age-matched, nonpregnant Hodgkin patients; pregnancy associated was defined as diagnosed during pregnancy and up to 3 months postpartum in this study. In another retrospective cohort study from a single hospital, Lishner et al. [32] identified 48 women who became pregnant 3 months prior to or up to 9 months after first treatment for Hodgkin lymphoma and 67 age-matched nonpregnant Hodgkin lymphoma cases. They observed no statistical difference in the 20-year survival or the distributions of stages at diagnosis between the pregnancy-associated Hodgkin lymphoma cases and their age-matched, nonpregnant cohort. Finally, a third study compared the prognosis of women diagnosed during pregnancy with Hodgkin lymphoma versus non-Hodgkin lymphoma at one hospital [18]. They noted that the clinical behavior of Hodgkin disease during pregnancy did not appear to differ from that outside of the pregnancy setting; however, the pregnancy-associated cases were not compared to a nonpregnant, age-matched cohort.
Non-Hodgkin Lymphoma
The prognosis of non-Hodgkin lymphoma during pregnancy is unclear due to very little primary data. Lishner et al. [33] reviewed the literature on retrospective series and case reports and concluded, “…there is evidence to suggest that pregnancy does not affect the course of [non-Hodgkin] lymphoma when properly treated.” Rapid clinical progression of pregnancy-associated non-Hodgkin lymphoma was reported in a series of 6 patients and review of 22 cases in the literature [50]; the affected patients were in advanced stage at diagnosis. Finally, significantly poorer prognosis was reported for women diagnosed during pregnancy with non-Hodgkin lymphoma patients compared to women diagnosed during pregnancy with Hodgkin lymphoma patients [18]; however, the cases were not compared to a nonpregnant cohort.
Horowitz et al. [22] conducted a systematic review of the literature published between 1967 and 2011 in order to determine the characteristics and outcomes of pregnancy-associated non-Hodgkin lymphoma. Women with pregnancy-associated non-Hodgkin lymphoma were significantly more likely to have highly aggressive (e.g., Burkitt lymphoma, immunoblastic lymphoma, and unspecified highly aggressive lymphomas) than aggressive lymphoma (e.g., diffuse large B-cell lymphoma and T-cell lymphomas) and an advanced stage of cancer at time of diagnosis. Extranodal involvement was observed in patients with advanced-stage pregnancy-associated non-Hodgkin lymphoma, which could be due to a later diagnosis of the cancer. The reproductive organs were the most common extranodal areas involved and may represent a unique characteristic of pregnancy-associated non-Hodgkin lymphoma as involvement of the reproductive organs is rarely observed in nonpregnant patients with this cancer. Finally, 6-month survival was 53 % for pregnancy-associated non-Hodgkin lymphoma patients. Patients with pregnancy-associated non-Hodgkin lymphoma treated prior to 2000 had significantly poorer 6- and 12-month survival (41.9 % and 36 %, respectively) than patients with pregnancy-associated non-Hodgkin lymphoma treated from 2000 to 2011 (6-month survival = 73 % and 12-month survival = 70 %).
Leukemia
There is general agreement in the literature that pregnancy does not influence the course of leukemia, but few primary data are presented or cited to support this position. Nicholson [41] concluded that there is no good evidence that pregnancy has a deleterious effect on leukemia, based on a review of five cases and the literature from 1959 to 1965. He calculated median survival rates of 5 months for acute leukemia (n = 98 cases) and 38 months for chronic myeloid leukemia (n = 44 cases); both survival rates were similar to survival rates of nonpregnant adult females. Catanzarite and Ferguson [9] conducted a review of the literature published from 1972 to 1982 of pregnant patients with acute leukemia. They estimated a median survival of 6–12 months postpartum for women diagnosed with acute leukemia during pregnancy, which they stated was consistent with survival for adults treated for acute leukemia. Finally, Chelghoum et al. [10] collected information via mailed questionnaire from 13 French centers that administered care to women diagnosed with acute leukemia during pregnancy. Based on the data from 37 cases from 1988 to 2003, they reported that overall survival rate was 65 % at 3 years and 46 % at 5 years and concluded that pregnancy does not affect the course of acute leukemia. None of the abovementioned studies of pregnancy-associated leukemia included a nonpregnant cohort.
A challenge in assessing the prognosis of leukemia diagnosed during pregnancy is selection bias. Leukemia has a rapid progression course and can be fatal without immediate treatment, and some women diagnosed with leukemia in the first trimester may elect to terminate their pregnancy [20]. Thus, the prognosis of pregnancy-associated leukemia would be based on a smaller sample of pregnant women diagnosed with cancer in the first trimester.
Ovarian Cancer and Pregnancy
Occurrence Rate During Pregnancy
Four population-based studies that addressed the rate of occurrence of pregnancy-associated ovarian cancer are reviewed [12, 21, 29, 49] (Table 1.2). The reported crude incidence rates of pregnancy-associated ovarian cancer were fairly similar across the four studies; however, no study specifically assessed the incidence rate of pregnancy-associated ovarian cancer over time. The crude incidence rate of ovarian cancer diagnosed during pregnancy only ranged from 0.9 to 1.8/100,000, about a twofold range. Differences in the rates of occurrence may occur based on what malignant ovarian cancer types are included in the analysis. For example, in a follow-up study to Smith et al. [49], Leiserowitz et al. [30] assessed the incidence rate of pregnancy-associated ovarian cancer versus the low malignant potential ovarian tumors. They reported an incidence rate for ovarian cancers of 1.8/100,000 births (87 cases). If the 115 cases diagnosed with tumors of low malignant potential are included, the incidence rate is 4.2/100,000 births (202 total cases); the crude incidence of diagnosis of ovarian cancer and tumors of low malignant potential during pregnancy only is 1.9/100,000 births as 90 cases were diagnosed during pregnancy only out of 4,858,505 births [30]. A comparable incidence rate of pregnancy-associated low malignant potential ovarian tumors was reported by Dgani et al. [12].
Impact of Pregnancy on Prognosis
Only one case-control study on the possible impact of pregnancy on the clinical course of ovarian cancer was identified in the medical literature. Stensheim et al. [51], a population-based study from Norway, reported no elevation in risk of cause-specific death (HR: 0.46; 95 % CI [0.17–1.23]) in patients diagnosed while pregnant. The comparable survival of ovarian cancer patients diagnosed during pregnancy and nonpregnant ovarian cancer patients may be due to the frequency of obstetric examinations (e.g., ultrasounds) during pregnancy.
Melanoma and Pregnancy
Occurrence Rate During Pregnancy
Four population-based studies that assessed the incidence of pregnancy-associated melanoma are reviewed [7, 14, 21, 49] (Table 1.2). The crude incidence rate of melanoma diagnosed during pregnancy only ranged from 0.6 to 14.9/100,000 births. A significant increase in the crude and age-adjusted incidence rates of pregnancy-associated melanoma was observed over time for a study from Sweden (1977–2006) [14]. A study in Australia reported a significant increase in the crude incidence rates, but not the age-adjusted rates, of pregnancy-associated melanoma from 1994 to 2007, which was attributed to increasing maternal age [7]. In particular, women aged 40–55 years old were at 7.55 times higher risk of pregnancy-associated melanoma as women aged 15–24 years [7]. The substantial differences in the estimated rates of pregnancy-associated melanoma between studies are not unexpected (Table 1.2), considering the differences in melanoma occurrence rates in different geographic regions, different age groups, and other maternal characteristics (e.g., geographical remoteness [7]). For example, the highest incidence rates of pregnancy-associated melanoma were reported for Australia, which is known to have the highest rates of melanoma in the world [7].
Impact of Pregnancy on Prognosis
Early reports suggested that pregnant patients with melanoma had more advanced lesions and shorter survival times than nonpregnant melanoma patients [26, 43]. However, the majority of case-control studies with longer follow-up evaluations reported no difference in survival between pregnancy-associated melanoma patients and their nonpregnant melanoma cohort [11, 27].
In a review of the literature, pregnancy-associated melanomas were often reported to have thicker tumors compared to nonpregnant patients, although this observation was not always statistically significant [27]. Thickness of the tumor has been identified as a significant predictor of survival in multivariate analyses in two separate studies [31, 48]. There is disagreement in the literature regarding whether pregnancy decreases the disease-free interval in melanoma patients with one case-control study reporting shorter disease-free interval for pregnancy-associated melanoma compared to nonpregnant patients [48], while others reported no significant effect of pregnancy status [35, 39].
The majority of studies report that survival of women diagnosed with melanoma during pregnancy is not different than nonpregnant women with melanoma. Leachman et al. [27] reviewed the available literature on the survival of pregnant versus nonpregnant melanoma patients and noted that stage I–II melanoma does not behave more aggressively in pregnant patients. They further noted that there were fewer reported cases of pregnant patients with stage III–IV melanoma; thus, it is unknown whether pregnancy may or may not influence the more advanced stages of this cancer type [27]. One recent population-based study in Norway reported a slightly elevated risk of cause-specific death (HR: 1.52; 95 % CI [1.01–2.31]) in patients diagnosed during pregnancy. The authors observed that the localization of the tumors were significantly different between the women diagnosed with melanoma during pregnancy (e.g., larger proportions of tumors on the head, neck, and trunk) compared to nonpregnant patients (e.g., larger proportion of tumors on the leg). Following adjustment for localization of the tumor, the hazard ratio for pregnant women was smaller (HR: 1.45; 95 % CI [0.96–2.21]), and the authors concluded their study was consistent with others that found that melanoma was not likely influenced by pregnancy-related hormones [51]. Pregnancy-associated melanoma patients also had no worse prognosis in cause-specific mortality than age-matched nonpregnant patients in a population-based study in Sweden, which adjusted for age, time period, parity, education, and tumor location [25].
Conclusions
Based on data from population-based studies, the incidence rate of pregnancy-associated cancer appears to have increased over time. This increase has been attributed, at least in part, to a trend for women to become pregnant later in their reproductive years. Of the seven cancer types reviewed, the incidence rates of breast cancer, melanoma, and non-Hodgkin lymphoma diagnosed in association with pregnancy appear to increase over time, while Hodgkin lymphoma has no temporal trend. Data on incidence rates across time are lacking for pregnancy-associated ovarian cancer and leukemia, and the rate of pregnancy-associated cervical cancer appears to increase or decrease depending on the population under study. Pregnancy does not appear to influence the progression of these seven cancers, with the possible exception of breast cancer. The observation of possibly poorer prognoses among pregnancy-associated breast cancer patients may be largely due to breast cancer patients being diagnosed with more advanced stages of cancer or diagnosed postpartum, which was not discussed in this chapter. The definition of pregnancy-associated cancer strongly influenced the resulting incidence rates. For example, the crude incidence rates for all the cancer types are substantially lower for cases diagnosed during pregnancy compared to incidence rates for cases diagnosed during pregnancy and up to 1 year following delivery. Future research on pregnancy-associated cancer should include an analysis of the timing of diagnosis to better understand any differences in incidence or prognosis between women diagnosed with cancer during pregnancy versus women diagnosed postpartum compared to a nonpregnant cancer patient cohort.
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