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Table of Contents
REVIEW ARTICLE
Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 61-70

Breast cancer and Fertility Part 2- Pregnancy Associated Breast Cancer


Department of Reproductive Medicine, Mother and Child Hospital, New Delhi, India

Date of Web Publication22-Feb-2019

Correspondence Address:
Nalini Mahajan
Mother and Child Hospital, D-59 Defence Colony, New Delhi - 110 024
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tofj.tofj_8_18

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  Abstract 


Pregnancy-associated breast cancer (PABC) refers to breast cancer (BC) diagnosed during pregnancy or within the first postpartum year. The increasing incidence follows the increase in age at first childbirth. Diagnostic delay due to physiological breast changes of pregnancy leads to the tumor being diagnosed at a more advanced stage. Since the termination of pregnancy does not alter the course of disease, patients can be offered BC management during pregnancy with a good outcome. Chemotherapy (CT) can be given safely during the second and third trimester of pregnancy. In the first trimester, the option of surgery is available while during puerperium, radiotherapy can be safely administered in addition to CT. Prognosis is related to the stage and grade of the tumor. Neonatal outcomes are reassuring. This article gives an overview of the diagnosis, management, and prognosis of PABC.

Keywords: Breast cancer, cancer survivor, chemotherapy, fertility preservation, pregnancy, pregnancy-associated breast cancer


How to cite this article:
Mahajan N. Breast cancer and Fertility Part 2- Pregnancy Associated Breast Cancer. Onco Fertil J 2018;1:61-70

How to cite this URL:
Mahajan N. Breast cancer and Fertility Part 2- Pregnancy Associated Breast Cancer. Onco Fertil J [serial online] 2018 [cited 2019 May 21];1:61-70. Available from: http://www.tofjonline.org/text.asp?2018/1/2/61/252693




  Introduction Top


Pregnancy-associated breast cancer (PABC) is defined as breast cancer (BC) diagnosed during pregnancy or within 1 year postpartum.[1],[2] It is considered to be the second most common cancer associated with pregnancy;[3] other common cancers in pregnancy being melanoma, hematological malignancies, and cervical cancer.[4],[5] PABC is reported in 1/10,000–1/3000 pregnancies and comprises 7% of all BCs in women under 45 years.[2],[6] A higher incidence of 15.6% has been reported for women below the age of 35 years.[7] The average age of onset of PABC is 33 years, and the average gestation at diagnosis is reported to be 21 weeks.[8] Almost 50% patients have a positive family history of BC, and 20%–30% of these young women are at risk of BRCA1/BRCA2 mutations.[9],[10] PABC is reported to be more aggressive and generally hormone receptor negative. The previously reported high rate of human epidermal growth factor receptor 2 (HER 2) overexpression has been contested. It has been suggested that the pathogenic pathway is probably different from that of non-PABCs. Pregnancy contributes to a delay in diagnosis and management; however, termination of pregnancy does not alter the course of disease.[11] Primary care physicians and obstetricians should have a high index of suspicion and must thoroughly evaluate pregnant women with suspicious breast symptoms or a breast lump that is present for more than 2 weeks. A trend to delay childbirth[12] and availability of ART to older women is projected to increase the incidence of PABC since the risk of BC increases with age. This article provides an overview of PABC symptoms, diagnosis, management, and prognosis that would be beneficial to reproductive medicine specialists and obstetricians confronted with such cases.


  Methods Top


This review uses published articles in the field of BC, fertility preservation (FP), PABC, and pregnancy after BC (PAFBC). Cited articles were found by a literature search using PubMed for articles published until September 2018. The reference lists of retrieved studies and review articles were also used to identify additional studies. Relevant society guidelines were studied. The following keywords were used: BC, breast tumor, PABC, fertility, FP, cancer survivor, chemotherapy (CT), and BRCA mutations.

Although the review article “BC and Fertility” was planned to be a series of two articles, the extensive literature and growing importance of PABC warrant an exclusive narration. The third part will deal with PAFBC.

Dual effect of pregnancy

The protective effect of pregnancy on BC is widely known;[13],[14] however, it has now come to light that this beneficial effect is conferred after many years of childbirth, before that women are in fact at an increased risk. This is known as the “dual effect” of pregnancy. The increased risk of BC after pregnancy peaks at 6 years after delivery and persists for approximately 10 years and is related to a woman's age at first childbirth, more importantly, time since first birth.[15] The change from BC promotion to protection or the “cross-over” effect is 3–5 years for young mothers aged 25 years or less, the risk being increased only marginally above that in nullipara.[16] Between 30 and 35 years, the risk increases and the crossover effect is delayed until the 60s. The age of 35 years has been recognized as a cutoff age. Full-term pregnancy before age 35 confers some protection while pregnancy after this age is associated with a permanent increase in BC risk.[14],[17],[18] The increased risk is believed to be due to the growth-promoting effects of pregnancy hormones on preexisting occult tumor cells.[19] The long-term protective effect is attributed to terminal differentiation of mammary stem cells which then become resistant or less sensitive to carcinogenic stimuli.[20],[21]

Presenting symptoms – the most common presentation is a palpable mass. Less common symptoms include diffuse breast enlargement, nipple discharge, focal pain, or unilateral milk rejection or refusal of the baby to feed from the affected breast. Hormonal changes during pregnancy and lactation lead to ductal and lobular growth, increased fluid content in breast tissue, and milk collection in the lobular acini prompting an increase in breast size, nodularity, and higher density of breast tissue.[22] This poses a problem for both clinical examination and diagnosis. These physiological breast changes often mask a small malignant growth; PABC is therefore generally detected at a more advanced stage of disease.[23] The differential diagnosis is from potentially benign conditions associated with pregnancy such as mastitis, fibroadenoma, galactocele, lobular hyperplasia, abscess, and fibrocystic disease.

Only 19% of all BCPs are diagnosed in the first trimester.[24] A low index of suspicion of cancer in pregnant women, adds to the diagnostic delay and a lag time of 1–13 months to diagnosis after appearance of symptoms, has been described.[25],[26] Woo et al. 2003[27] reported a 1–3-month diagnostic delay during pregnancy and lactation with a median tumor size of 3.5 cm at diagnosis. Delay in diagnosis leads to delay in starting treatment which in turn increases risk of metastasis. Deferring treatment by 1 month has been shown to increase the risk of axillary metastasis by 0.9%–1.8%.[28]

Risk factors

Factors which increase the risk of PABC include

  1. Age at first childbirth – If first childbirth is delayed beyond 35 years, it leads to a permanent increase in BC risk compared to nulliparous women[13],[18],[29]
  2. Number of pregnancies – BC risk decreases with multiple pregnancies
  3. BRCA mutations – Carriers of BRCA1 and BRCA2 mutation do not have an increased risk of developing PABC compared with noncarriers.[30] They are however not protected from BC even if their first childbirth is at a young age.[31] In young women with triple-negative BC, the probability of detecting a germline BRCA mutation is approximately 20%[10]
  4. Effect of lactation – McCready et al. 2014[32] reported that BC diagnosed during lactation is more aggressive and leads to a poorer prognosis. A shorter time to relapse, increased risk of metastasis, and death are seen in women who are diagnosed with BC within a year of delivery.[18],[33] The lactating breast tissue expresses higher cytokine levels that promote growth and angiogenesis, leading to rapid tumor progression[34]
  5. Changes in breast tissue – Hormonal and immune system changes in pregnancy are implicated in the promotion of tumor growth. Elevated hormones and growth factors during pregnancy and lactation responsible for ductal and lobular growth allow for rapid tumor progression from early to advanced lesions and aggressive metastatic disease.[35],[36] Pro-inflammatory processes that are initiated in the breast tissue during this period also contribute to the development and progression of PABC.[19] Unrestricted growth of malignant cells may also occur due to immune system alterations that occur in pregnancy to protect the fetal semiallograft.[37]


Diagnosis

Imaging

Ultrasound (USG) is the first-line imaging modality used for diagnosis in pregnant and lactating young women. If breast USG is nonconfirmatory, or there are suspicious findings, mammography (MMG) or digital breast tomosynthesis may be indicated. The role of advanced imaging techniques such as dynamic contrast-enhanced magnetic resonance imaging (DCE–MRI) in pregnancy is limited although it can be used during lactation. There is no role for molecular breast imaging using Tc-99 m Sestamibi during pregnancy or lactation.[38] MMG and MRI are useful in confirming locoregional staging and satellite lesions [Table 1]a,[Table 1]b,[Table 1]-c].
Table 1: Imaging in Pregnancy Associated Breast Cancer. ACR Appropriateness Criteria (38)

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Ultrasound

USG is considered the gold standard for detection and characterization of breast masses in pregnant women.[39]

MMG is safe in pregnancy although its accuracy is limited due to an increase in water content and change in fat distribution in the breast. It is helpful in the detection of microcalcifications. The International Commission on Radiological Protection (ICRP) (2000) has stated that “prenatal doses from most properly done diagnostic procedures present no measurably increased risk of prenatal death, malformation, or impairment of mental development over the background incidence of these entities” and that fetal doses below 100 mGy should not be considered a reason for terminating a pregnancy. The fetal radiation dose from a 4-view mammogram is <0.03 mGy. No teratogenic effects have been demonstrated below 50 mGy.[40] Diagnostic breast imaging during pregnancy with appropriate abdominal shielding, is advised to confirm clinical suspicion and for locoregional staging.[41]

Magnetic resonance imaging

The physiologically increased breast vascularity of pregnancy and lactation may limit the sensitivity of DCE breast MRI. Although physiological hypervascularization of pregnancy poses a challenge, contrast MRI imaging is able to detect carcinomatous and satellite lesions in lactating women.[22] Since gadolinium agents used for contrast cross the placenta, their safety in pregnancy has not been established; they should be used only when benefit outweighs the risk. The American College of Radiology (ACR)[38] does not recommend the intravenous administration of gadolinium during pregnancy. The use of diffusion tensor imaging is being investigated to overcome this problem.[42] Postpartum MRI poses no such problem and breastfeeding can be continued safely.[22]

Tissue diagnosis

For tissue diagnosis, core needle or excision biopsy is the gold standard. A needle biopsy though sensitive has an increased risk of false positives due to atypia inherent to secretory changes in breast tissue during pregnancy and lactation.[31] There is an increased risk of bleeding and milk fistula formation. Histological grade, receptor status, and HER2 information are mandatory.

Chest X-ray and ultrasound of the liver

These are used to detect metastatic lesions. Fetal exposure from a chest X-ray is low being about 0.1 mGy.

Histopathology

PABC tend to be high-grade, poorly differentiated tumors with lymphovascular invasion and nodal involvement[30],[31],[43],[44] at diagnosis, particularly those diagnosed during lactation.[5],[45] Aziz et al.[43] reported that invasive ductal adenocarcinoma BC was the most frequently occurring histological type seen in 75%–90% of cases, followed by invasive lobular and rarely inflammatory subtype. Regarding receptor status, PABC exhibit a higher incidence of negative receptor (ER, PR) status.[46],[47] Controversy exists regarding HER2 overexpression in PABC. A study conducted by Murphy et al.[44] states that there is no difference in HER2 status between PABC and age-matched controls. Some recent studies suggest that there is no difference in tumor size, node involvement, grading, hormonal status, or lymphovascular invasion between PABC and BC not associated with pregnancy.[44],[48] Placental metastasis is rare but indicates poor maternal prognosis. Pathological assessment of the placenta after delivery is recommended.[31]

Treatment

A study by de Haan et al. 2018[49] reveals that over the years, the proportion of PABC patients who received antenatal care and CT treatment has shown an increase. PABC present a challenge for treatment as one needs to draw a fine balance between the health of the mother and child. Treatment is based on the stage and type of tumor and the gestational age at diagnosis. It is possible to use surgery, CT, and radiation therapy (RT) depending on the period of gestation. Maternal and fetal safety and well-being mandate the involvement of a multidisciplinary team. The general recommendations for the BC management during pregnancy are shown in [Table 2].
Table 2: Pregnancy-associated breast cancer treatment overview

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  1. Surgery can be performed in all trimesters
  2. CT in the second and third trimesters
  3. Radiotherapy only in the postpartum period.


Surgical treatment

Surgery is considered to be safe during pregnancy and is the only treatment that can be offered during the first trimester. General principles that direct surgery for BC are applicable to PABC as well. Mastectomy is the preferred procedure although breast-conserving surgery (BCS) is also gaining popularity.[50] BCS does not increase risk of recurrence[51] or pregnancy complications and the overall survival (OS) is similar to patients with radical mastectomy;[52] however, subsequent radiotherapy is mandatory.[53] BCS may be performed safely if RT can be delayed till the postpartum period. Chen et al.[54] in a meta-analysis calculated an absolute increase in the risk of local recurrence, of 1% per month of delay in starting RT. However, there is often a delay of 6 months to RT even in nonpregnant patients, as they are receiving CT after BCS.[55]

Axillary staging is important as it influences prognosis, and axillary clearance is done for patients with lymph node-positive disease. Sentinel lymph node (SLN) biopsy is preferable to elective axillary LN dissection for staging as it has a lower morbidity, the lymphedema being 5.3% versus 11.8%, respectively.[51] The use of SLN biopsy in patients with early disease is subject to controversy due to the risk of radiation exposure to fetus and safety of the blue dye used. SLN or the first draining node is identified by injection of a blue dye (isosulfan blue/methylene blue) and/or a radiolabelled colloid (e.g., technetium Tc 99 m sulfur colloid) at the primary tumor site. Studies suggest that 99 m-Technitium (Tc99m) injection at a conventional dose between 12.1 and 18.5MBq exposes the fetus to an irradiation dose between 0.011 and 0.0245 mSv which is much below the recommended threshold of 50 mSv. The injected Tc99m is localized in the SLN most of it remaining trapped at the injection site on the breast or within the lymphatics.[56] Gentilini et al. 2010[51] reported the use of SLNB in pregnant patients including patients in 1st trimester from 2001 to 2007 and found no increase in pregnancy complications, birth weight, or fetal congenital malformations. Other authors have suggested that using a 1-day protocol exposes the fetus to a radiation dose that does not exceed 0.45 mGy.[50],[52],[57] Technetium does not pass the placental barrier, and its use has been recommended by the European international guidelines[58] but not by the American Society of Clinical Oncology guidelines (2017).[59] The ICRP states that termination of pregnancy is seldom required for most common procedures in diagnostic nuclear medicine, and there should be no hesitation in advising such procedures in pregnancy if indicated.[40] The use of blue dye (isosulfan blue or methylene blue) a pregnancy category – C drug, is not recommended. Isosulfan can lead to anaphylactic reaction (1%–2%) while methylene blue leads to fetal demise and jejunal atresia in the first trimester due to vasoconstrictive effects in blocking nitric oxide.[49],[60] Decisions on SLN and type of surgery require individualization.

Although studies suggest that surgery does not increase the risk of miscarriage compared to the background risk of SAB in the general population,[53],[61] many surgeons prefer to wait till the end of first trimester to do surgery. Breast reconstruction surgery (BRS) is avoided till breast involution after delivery for best cosmetic results.[62] Lohsiriwat et al. 2013[63] performed immediate BRS with expander on 78 patients who underwent mastectomy during pregnancy and reported excellent pregnancy outcomes without obstetrical complications after surgery.

Radiation therapy

RT is generally delayed till the postpartum period to avoid radiation exposure to the fetus.[64],[65],[66] Effects of RT on the fetus can be deterministic (teratogenic) - which is dose dependent or stochastic (carcinogenic) which may not be related to RT dose. Radiation exposure in early pregnancy leads to abortion or malformation while later exposure can lead to neuropsychological dysfunction due to effects on CNS development. Childhood leukemia appears to be the main stochastic effect, an increased relative risk of 1.4 is seen at a dose of 10 mGy. If required, RT can be given in the first and early second trimester after counseling. With appropriate shielding of the abdomen, radiation dose to the fetus is low around 0.1% to 0.3% of dose to the breast, giving a very low malformation risk.[65],[66],[67]

Chemotherapy during pregnancy

Most CT agents fall into category D or X which means that teratogenic effects in humans have been reported, but drugs can be used if benefits outweigh risk. The recommendation for CT in PABC is to broadly follow the guidelines for treatment of nonpregnant young patients with BC during the second and third trimester. Both adjuvant and neoadjuvant CT can be administered. CT is contraindicated in the first trimester due to major teratogenic effects on fetus reported at 14%–18%.[11],[66] In the 2nd and 3rd trimester, however, the reported fetal malformation for CT exposure is 3.8% which is similar to the congenital malformation rate in the general population.[68]

The standard adjuvant or neoadjuvant therapy administered is anthracyclines, cyclophosphamide, and taxanes. Epirubicin hydrochloride-cyclophosphamide followed by weekly paclitaxel is the most widely used regime. 5 fluorouracil was also used in BC earlier; however, addition of 5-FU to the anthracyclin-taxane regime has not added any benefit and its use is not advocated in BC.[66],[69] The data on safety of taxanes are limited although authors have reported no increase in maternal or fetal complications.[44],[49],[70],[71] Gadducci et al. 2003[70] reported that taxanes and anthracyclines delivery to the fetus may be restricted by the placental barrier confirming that they can be used safely during pregnancy. The safety of taxanes has been questioned by Mir et al. 2010[72] who reported its association with risk of congenital malformation. Since data on taxanes are limited, it has been proposed by some authors that use of taxanes should be individualized[53] and that they may be used in anthracycline-resistant cases or after delivery.[11] Carboplatin and cisplatin have been used in neoadjuvant therapy and give a higher response.[73] Carboplatin appears to have less toxicity than cisplatin.[66]

Dose-dense therapy (DDT) (same dose given at a shorter interval) or intensified dose-dense therapy (IDD) (higher dose at a shorter interval) gives better survival rates more so in high-risk patients.[72],[73],[74] DDT does not increase maternal or fetal complications and gives the same overall survival (OS) rate at 3.5 years as conventional therapy.[68] IDD leads to a high rate of bone marrow suppression and cannot be recommended in pregnancy.[75]

Dosage

It is based on the patient's body surface area calculated by weight, for both pregnant and nonpregnant patients. Even though serum levels of taxanes have been found to be lower in pregnant patients,[76] an increase in dosage is not advised.[66] Anthracycline levels on the other hand are not altered in pregnancy.

Side effects of chemotherapy

The most common maternal side effects experienced are neutropenia, mouth ulcers, anaphylaxis, constipation, tachycardia, and arm cellulitis.

Biological agents

Biological agents such as Trastuzumab which is the specific drug used for HER 2-positive BC is contraindicated in pregnancy due to high risk of oligoamnios and prematurity.[77] Fetal respiratory insufficiency and fetal heart failure have also been reported.[78] Oligoamnios corrects itself when the drug is stopped. Trastuzumab may be considered in a high-risk pregnancy but an informed decision is mandatory before use. Inadvertent fetal exposure to 1–2 cycles of trastuzumab should not be an indication for pregnancy termination. No data are available for the use of pertuzumab, which when added to trastuzumab improves tumor response.

Hormone therapy

Tamoxifen and other selective estrogen receptor modulators (SERMs) used in hormone receptor-positive BC are contraindicated in pregnancy. Tamoxifen can lead to birth defects such as ambiguous genitalia and craniofacial malformations.[79]

Supportive treatment

Supportive treatment of CT is given as per general recommendations. 5-hydroxytryptamine antagonists such as ondansetron (category B) and promethazine (category C) given before CT are administered routinely in pregnancy for hyperemesis. Among the corticosteroids, methylprednisolone (category C) and hydrocortisone (category C) are preferred as they do not cross the placenta.[53] First-trimester use of corticosteroids is associated with increased risk of cleft palate.[80] Granulocyte colony-stimulating growth factor (category C) and erythropoietin (category C) have been safely administered in pregnant patients.[81]

Obstetric complications

In utero exposure to CT is associated with a small increase in the risk of preterm rupture of membranes (3% vs. 0%)[24] and preterm labor (6% vs. 2%).[49],[82] Premature delivery should be avoided as far as possible since prematurity is the major cause for neuropsychological dysfunction. de Haan et al. 2018[49] reported a relationship between antenatal platinum-based CT and small for gestational age and an increase in NICU admissions with taxane exposure. Maxwell et al. 2018[3] reported comparable obstetric outcomes for women with gestational BC as compared to those with pregestational BC. They observed that induction of labor and preterm birth were more common in women with gestational BC to facilitate postpartum treatment.

Antenatal care

Pregnant patients should be monitored in high-risk obstetric units with a multidisciplinary team, which should include an obstetrician, a fetal medicine specialist, neonatologist, medical and surgical oncologist, and a geneticist to achieve the best outcome. Standard protocol for antenatal care is followed; closer monitoring is recommended if pregnancy complications such as hypertension or gestational diabetes are present.[78] A baseline USG for dating and serial Doppler studies should be carried out every 3 weeks to estimate the date of delivery and evaluate for intrauterine growth restriction (IUGR). Detailed anomaly scan at 20 weeks is important to look for any preexisting malformations. Delivery should be effected as close to term as possible. CT should be stopped at 35 weeks' gestation; a 2–3 week interval should be kept between the last CT cycle and delivery to prevent myelosuppression in both mother and fetus and to avoid drug accumulation in the fetus.[79] Genetic counseling and BRCA testing should be offered to women with BC in pregnancy. Obstetric indications should dictate the need for cesarean section. It is mandatory to send the placenta for HPE after delivery. For fetal monitoring during surgery, recommendations of the American College of Obstetricians and Gynecologists should be followed.[83]

Postpartum

Both CT and RT can be started immediately after a vaginal delivery and a week after a cesarean section.

Breastfeeding

Breastfeeding is contraindicated during treatment with CT because many of the drugs are excreted in milk and also during RT.[79],[84]

Neonatal complications

Studies confirm that there are no significant neonatal complications after antenatal CT. In two prospective studies on long-term follow-up of children exposed to intrauterine CT, no clinical difference in neurocognitive or cardiac development was seen between the treatment and the control group. An association with small for dates/gestational age has been found in some studies[24],[79],[85],[86] although other authors have not been able to confirm this.[12] Reassuring cardiac outcomes have been reported in children who were exposed to anthracycline during antenatal period.[87] The effect of antenatal CT on secondary malignant diseases or fertility later in life is unclear[49]

Pregnancy termination

BC during pregnancy is viewed with a great deal of apprehension because of the perceived effects of pregnancy on cancer prognosis and the challenge of antenatal cancer treatment. Pregnancy termination is often advised or sought when the tumor is diagnosed in early pregnancy. Many studies have shown that early termination does not improve outcome.[88],[89] Similar survival rates were found in women with PABC who terminated pregnancy, had spontaneous abortion, or went on to deliver.[88] Termination may be advised in case of advanced disease or aggressive tumors diagnosed in first trimester due to the risk of teratogenicity with chemotherapeutic agents.[31] The decision to terminate pregnancy has to be made by the patient after receiving complete information on her options, prognosis, and possible risks of CT exposure to the fetus.

Prognosis

The prognosis of PABC is subject to controversy while some studies have observed a poorer survival among women with PABC;[90],[91],[92] other studies suggest that pregnancy per se does not worsen the prognosis of BC if appropriate treatment is administered in time.[7],[44],[66],[85],[93] The tumor is generally picked up at a more advanced stage during pregnancy which leads to the poorer outcome reported.[7],[44],[66],[85],[93] Bonnier et al. 1997[94] reported a poorer outcome for PABC cases matched for age and year of diagnosis although the impact of pregnancy on OS was not statistically significant in their study. Rodriguez 2008[92] in a large registry-based study (California cancer registry 1991–99) compared 797 PABC cases and 4177 age-matched controls concluded that when controlled for stage, race, and hormone receptor status, PABC cases had a slightly higher risk (14%) of death, even when only localized-stage disease was considered. In contrast, a retrospective analysis conducted by Murphy et al. 2012[44] comparing PABC and non-PABC patients concluded that recent PABC was independently associated with more adverse pathologic features in young women; however, after controlling for age and stage of disease, PABC in itself was not a negative prognostic factor (P = 0.1317). The independent prognostic factors for OS were estrogen receptor status (P = 0.0031) and N class (P = 0.0003). The OS did not differ between groups at a median follow-up of 6.3 years for cases and 4.7 years for controls (P = 0.0787).

A more recent publication by Johansson et al. 2018[93] examined clinicopathologic features and survival in women with PABC. A cohort of women aged 15–44 years diagnosed with invasive BC between 1992 and 2009 was identified in the Swedish Cancer Register and the BC Quality Registers. Age, tumor stage, Elston grade, and receptor status were compared between nulliparous women and women with BC during pregnancy and up to 10 years postdelivery. The study included 1,661 nulliparous women with BC, 778 women with PABC (97 during pregnancy, 270 in the first and 411 in the 2nd year after delivery) and 3598 during 2–10 years postdelivery. Compared to nulliparous women, women with PABC, especially those diagnosed 0–12 months after delivery, had more advanced T and N stage and higher proportions of ER/PR negative, HER2 positive, and triple-negative tumors. The poorest prognostic characteristics were observed in the first 6 months' postpartum. After adjusting for age, year, education, and region, an increased hazard ratios (HR) was observed in women diagnosed within 5 years of delivery. The HR became nonsignificant after making additional adjustment for tumor characteristics. The authors concluded that the poorer prognosis observed in women with PABC appears to be largely explained by more adverse tumor characteristics at diagnosis.


  Conclusion Top


Pregnancy-associated BC is being encountered more frequently due to a trend in increasing age at first birth and availability of ART to women in the fourth and fifth decade of life. The diagnosis is often delayed due to physiological breast changes, and physicians should be more vigilant not to miss the diagnosis. PABC patients tend to have higher grade, receptor-negative, and poorly differentiated tumors, particularly those diagnosed during lactation. Diagnosis can be made by USG and MMG. DCE-MRI is contraindicated in pregnancy but can be used during lactation.

The management of PABC should be based on the stage and grade of tumor stage and the gestational age at diagnosis. The challenge is to treat maternal disease while maintaining the safety and health of the baby. Surgery is the only treatment option in the first trimester; CT with anthracyclines and taxanes can be given in the second and third trimester without an increase in risk of fetal congenital malformations. DDT can also be administered safely. On the other hand, RT is given preferentially after delivery. CT should be stopped at 35 weeks of pregnancy to avoid myelosuppression. The obstetrical management of PABC requires the involvement of a multidisciplinary team for a good outcome. Close antenatal monitoring in a high-risk unit is mandatory as there is an increased risk of IUGR and preterm labor. Delivery should be conducted as close to term as possible to avoid neonatal effects subsequent to prematurity. Breastfeeding is contraindicated during CT or RT.

The poorer prognosis of PABC is related to the advanced stage at diagnosis and treatment delays rather than pregnancy. The poorest prognostic characteristics are observed in the first 6 months' postpartum. Pregnancy termination does not change the course of disease or the OS rate. With a change in societal structure and professional aspirations of women, the stage is set for an increase in PABC making it important for the obstetricians to be well prepared to handle these challenging situations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
RCOG Green-top Guideline No. 12. Pregnancy and Breast Cancer. UK Royal College of Obstetricians and Gynaecologists; 2011.  Back to cited text no. 1
    
2.
Andersson TM, Johansson AL, Hsieh CC, Cnattingius S, Lambe M. Increasing incidence of pregnancy-associated breast cancer in Sweden. Obstet Gynecol 2009;114:568-72.  Back to cited text no. 2
    
3.
Maxwell CV, Al-Sehli H, Parrish J, D'Souza R. Breast cancer in pregnancy: A retrospective cohort study. Gynecol Obstet Invest 2018:1-7.  Back to cited text no. 3
    
4.
Genin AS, De Rycke Y, Stevens D, Donnadieu A, Langer A, Rouzier R, et al. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases. Breast 2016;30:222-7.  Back to cited text no. 4
    
5.
Stensheim H, Møller B, van Dijk T, Fosså SD. Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: A registry-based cohort study. J Clin Oncol 2009;27:45-51.  Back to cited text no. 5
    
6.
Johansson AL, Andersson TM, Hsieh CC, Cnattingius S, Lambe M. Increased mortality in women with breast cancer detected during pregnancy and different periods postpartum. Cancer Epidemiol Biomarkers Prev 2011;20:1865-72.  Back to cited text no. 6
    
7.
Beadle BM, Woodward WA, Middleton LP, Tereffe W, Strom EA, Litton JK, et al. The impact of pregnancy on breast cancer outcomes in women<=35 years. Cancer 2009;115:1174-84.  Back to cited text no. 7
    
8.
Navrozoglou I, Vrekoussis T, Kontostolis E, Dousias V, Zervoudis S, Stathopoulos EN, et al. Breast cancer during pregnancy: A mini-review. Eur J Surg Oncol 2008;34:837-43.  Back to cited text no. 8
    
9.
Valentini A, Lubinski J, Byrski T, Ghadirian P, Moller P, Lynch HT, et al. The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation. Breast Cancer Res Treat 2013;142:177-85.  Back to cited text no. 9
    
10.
Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 2015;33:304-11.  Back to cited text no. 10
    
11.
Martínez MT, Bermejo B, Hernando C, Gambardella V, Cejalvo JM, Lluch A, et al. Breast cancer in pregnant patients: A review of the literature. Eur J Obstet Gynecol Reprod Biol 2018;230:222-7.  Back to cited text no. 11
    
12.
Lee YY, Roberts CL, Dobbins T, Stavrou E, Black K, Morris J, et al. Incidence and outcomes of pregnancy-associated cancer in Australia, 1994-2008: A population-based linkage study. BJOG 2012;119:1572-82.  Back to cited text no. 12
    
13.
Rosner B, Colditz GA, Willett WC. Reproductive risk factors in a prospective study of breast cancer: The nurses' health study. Am J Epidemiol 1994;139:819-35.  Back to cited text no. 13
    
14.
Albrektsen G, Heuch I, Tretli S, Kvåle G. Breast cancer incidence before age 55 in relation to parity and age at first and last births: A prospective study of one million Norwegian women. Epidemiology 1994;5:604-11.  Back to cited text no. 14
    
15.
Albrektsen G, Heuch I, Hansen S, Kvåle G. Breast cancer risk by age at birth, time since birth and time intervals between births: Exploring interaction effects. Br J Cancer 2005;92:167-75.  Back to cited text no. 15
    
16.
Albrektsen G, Heuch I, Kvåle G. The short-term and long-term effect of a pregnancy on breast cancer risk: A prospective study of 802,457 parous Norwegian women. Br J Cancer 1995;72:480-4.  Back to cited text no. 16
    
17.
Trichopoulos D, Hsieh CC, MacMahon B, Lin TM, Lowe CR, Mirra AP, et al. Age at any birth and breast cancer risk. Int J Cancer 1983;31:701-4.  Back to cited text no. 17
    
18.
Borges VF, Schedin PJ. Pregnancy-associated breast cancer: An entity needing refinement of the definition. Cancer 2012;118:3226-8.  Back to cited text no. 18
    
19.
Schedin P. Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer 2006;6:281-91.  Back to cited text no. 19
    
20.
Lambe M, Hsieh C, Trichopoulos D, Ekbom A, Pavia M, Adami HO, et al. Transient increase in the risk of breast cancer after giving birth. N Engl J Med 1994;331:5-9.  Back to cited text no. 20
    
21.
Miller WR. Hormonal factors and risk of breast cancer. Lancet 1993;341:25-6.  Back to cited text no. 21
    
22.
Taron J, Fleischer S, Preibsch H, Nikolaou K, Gruber I, Bahrs S, et al. Background parenchymal enhancement in pregnancy-associated breast cancer: A hindrance to diagnosis? Eur Radiol 2018. Available from: https://doi.org/10.1007/s00330-018-5721-7. [Last accessed on 2018 Nov 15].  Back to cited text no. 22
    
23.
Ishida T, Yokoe T, Kasumi F, Sakamoto G, Makita M, Tominaga T, et al. Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation: Analysis of case-control study in Japan. Jpn J Cancer Res 1992;83:1143-9.  Back to cited text no. 23
    
24.
Loibl S, Han SN, von Minckwitz G, Bontenbal M, Ring A, Giermek J, et al. Treatment of breast cancer during pregnancy: An observational study. Lancet Oncol 2012;13:887-96.  Back to cited text no. 24
    
25.
Johansson AL, Andersson TM, Hsieh CC, Jirström K, Dickman P, Cnattingius S, et al. Stage at diagnosis and mortality in women with pregnancy-associated breast cancer (PABC). Breast Cancer Res Treat 2013;139:183-92.  Back to cited text no. 25
    
26.
Kim YG, Jeon YW, Ko BK, Sohn G, Kim EK, Moon BI, et al. Clinicopathologic characteristics of pregnancy-associated breast cancer: Results of analysis of a nationwide breast cancer registry database. J Breast Cancer 2017;20:264-9.  Back to cited text no. 26
    
27.
Woo JC, Yu T, Hurd TC. Breast cancer in pregnancy: A literature review. Arch Surg 2003;138:91-8.  Back to cited text no. 27
    
28.
Viswanathan S, Ramaswamy B. Pregnancy-associated breast cancer. Clin Obstet Gynecol 2011;54:546-55.  Back to cited text no. 28
    
29.
Rosner B, Colditz GA. Nurses' health study: Log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst 1996;88:359-64.  Back to cited text no. 29
    
30.
Bell RJ, Fradkin P, Parathithasan N, Robinson PJ, Schwarz M, Davis SR, et al. Pregnancy-associated breast cancer and pregnancy following treatment for breast cancer, in a cohort of women from Victoria, Australia, with a first diagnosis of invasive breast cancer. Breast 2013;22:980-5.  Back to cited text no. 30
    
31.
Padmagirison R, Gajjar K, Spencer C. Management of breast cancer during pregnancy. Obstet Gynecol 2010;12:186-92.  Back to cited text no. 31
    
32.
McCready J, Arendt LM, Glover E, Iyer V, Briendel JL, Lyle SR, et al. Pregnancy-associated breast cancers are driven by differences in adipose stromal cells present during lactation. Breast Cancer Res 2014;16:R2.  Back to cited text no. 32
    
33.
Halaska MJ, Pentheroudakis G, Strnad P, Stankusova H, Chod J, Robova H, et al. Presentation, management and outcome of 32 patients with pregnancy-associated breast cancer: A matched controlled study. Breast J 2009;15:461-7.  Back to cited text no. 33
    
34.
Yu HH, Cheung PS, Leung RC, Leung TN, Kwan WH. Current management of pregnancy-associated breast cancer. Hong Kong Med J 2017;23:387-94.  Back to cited text no. 34
    
35.
Gupta PB, Proia D, Cingoz O, Weremowicz J, Naber SP, Weinberg RA, et al. Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Res 2007;67:2062-71.  Back to cited text no. 35
    
36.
Polivka J Jr., Altun I, Golubnitschaja O. Pregnancy-associated breast cancer: The risky status quo and new concepts of predictive medicine. EPMA J 2018;9:1-3.  Back to cited text no. 36
    
37.
Shakhar K, Valdimarsdottir HB, Bovbjerg DH. Heightened risk of breast cancer following pregnancy: Could lasting systemic immune alterations contribute? Cancer Epidemiol Biomarkers Prev 2007;16:1082-6.  Back to cited text no. 37
    
38.
Expert Panel on Breast Imaging, diFlorio-Alexander RM, Slanetz PJ, Moy L, Baron P, Didwania AD, et al. ACR appropriateness criteria® breast imaging of pregnant and lactating women. J Am Coll Radiol 2018;15:S263-75.  Back to cited text no. 38
    
39.
Vashi R, Hooley R, Butler R, Geisel J, Philpotts L. Breast imaging of the pregnant and lactating patient: Imaging modalities and pregnancy-associated breast cancer. AJR Am J Roentgenol 2013;200:321-8.  Back to cited text no. 39
    
40.
The 2007 recommendations of the international commission on radiological protection. ICRP publication 103. Ann ICRP 2007;37:1-332.  Back to cited text no. 40
    
41.
NCCN Clinical Practice Guidelines in Oncology. Breast Cancer Screening and Diagnosis. Version 1; 2016. Available from: https://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf. [Last accessed on 2018 Nov 20].  Back to cited text no. 41
    
42.
Nissan N, Furman-Haran E, Allweis T, Menes T, Golan O, Kent V, et al. Noncontrast breast MRI during pregnancy using diffusion tensor imaging: A feasibility study. J Magn Reson Imaging 2019;49:508-17.  Back to cited text no. 42
    
43.
Aziz S, Pervez S, Khan S, Siddiqui T, Kayani N, Israr M, et al. Case control study of novel prognostic markers and disease outcome in pregnancy/lactation-associated breast carcinoma. Pathol Res Pract 2003;199:15-21.  Back to cited text no. 43
    
44.
Murphy CG, Mallam D, Stein S, Patil S, Howard J, Sklarin N, et al. Current or recent pregnancy is associated with adverse pathologic features but not impaired survival in early breast cancer. Cancer 2012;118:3254-9.  Back to cited text no. 44
    
45.
Middleton LP, Amin M, Gwyn K, Theriault R, Sahin A. Breast carcinoma in pregnant women: Assessment of clinicopathologic and immunohistochemical features. Cancer 2003;98:1055-60.  Back to cited text no. 45
    
46.
Pilewskie M, Gorodinsky P, Fought A, Hansen N, Bethke K, Jeruss J, et al. Association between recency of last pregnancy and biologic subtype of breast cancer. Ann Surg Oncol 2012;19:1167-73.  Back to cited text no. 46
    
47.
Genin AS, Lesieur B, Gligorov J, Antoine M, Selleret L, Rouzier R, et al. Pregnancy-associated breast cancers: Do they differ from other breast cancers in young women? Breast 2012;21:550-5.  Back to cited text no. 47
    
48.
Mathelin C, Annane K, Treisser A, Chenard MP, Tomasetto C, Bellocq JP, et al. Pregnancy and post-partum breast cancer: A prospective study. Anticancer Res 2008;28:2447-52.  Back to cited text no. 48
    
49.
de Haan J, Verheecke M, Van Calsteren K, Van Calster B, Shmakov RG, Mhallem Gziri M, et al. Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: A 20-year international cohort study of 1170 patients. Lancet Oncol 2018;19:337-46.  Back to cited text no. 49
    
50.
Khera SY, Kiluk JV, Hasson DM, Meade TL, Meyers MP, Dupont EL, et al. Pregnancy-associated breast cancer patients can safely undergo lymphatic mapping. Breast J 2008;14:250-4.  Back to cited text no. 50
    
51.
Gentilini O, Cremonesi M, Toesca A, Colombo N, Peccatori F, Sironi R, et al. Sentinel lymph node biopsy in pregnant patients with breast cancer. Eur J Nucl Med Mol Imaging 2010;37:78-83.  Back to cited text no. 51
    
52.
Kuerer HM, Gwyn K, Ames FC, Theriault RL. Conservative surgery and chemotherapy for breast carcinoma during pregnancy. Surgery 2002;131:108-10.  Back to cited text no. 52
    
53.
Krishna I, Lindsay M. Breast cancer in pregnancy. Obstet Gynecol Clin North Am 2013;40:559-71.  Back to cited text no. 53
    
54.
Chen Z, King W, Pearcey R, Kerba M, Mackillop WJ. The relationship between waiting time for radiotherapy and clinical outcomes: A systematic review of the literature. Radiother Oncol 2008;87:3-16.  Back to cited text no. 54
    
55.
Toesca A, Gentilini O, Peccatori F, Azim HA Jr., Amant F. Locoregional treatment of breast cancer during pregnancy. Gynecol Surg 2014;11:279-84.  Back to cited text no. 55
    
56.
Balaya V, Bonsang-Kitzis H, Ngo C, Delomenie M, Gosset M, Mimouni M, et al. What about sentinel lymph node biopsy for early breast cancer during pregnancy? J Gynecol Obstet Hum Reprod 2018;47:205-7.  Back to cited text no. 56
    
57.
Zubor P, Kubatka P, Kapustova I, Miloseva L, Dankova Z, Gondova A, et al. Current approaches in the clinical management of pregnancy-associated breast cancer-pros and cons. EPMA J 2018;9:257-70.  Back to cited text no. 57
    
58.
Peccatori FA, Azim HA Jr., Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, et al. Cancer, pregnancy and fertility: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24 Suppl 6:vi160-70.  Back to cited text no. 58
    
59.
Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2014;32:1365-83.  Back to cited text no. 59
    
60.
Pruthi S, Haakenson C, Brost BC, Bryant K, Reid JM, Singh R, et al. Pharmacokinetics of methylene blue dye for lymphatic mapping in breast cancer-implications for use in pregnancy. Am J Surg 2011;201:70-5.  Back to cited text no. 60
    
61.
Walton JR, Prasad MR. Obstetric and neonatal outcomes of cancer treated during pregnancy. Clin Obstet Gynecol 2011;54:567-73.  Back to cited text no. 61
    
62.
Ji YI, Kim KT. Gynecologic malignancy in pregnancy. Obstet Gynecol Sci 2013;56:289-300.  Back to cited text no. 62
    
63.
Lohsiriwat V, Peccatori FA, Martella S, Azim HA Jr., Sarno MA, Galimberti V, et al. Immediate breast reconstruction with expander in pregnant breast cancer patients. Breast 2013;22:657-60.  Back to cited text no. 63
    
64.
Huang J, Barbera L, Brouwers M, Browman G, Mackillop WJ. Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol 2003;21:555-63.  Back to cited text no. 64
    
65.
Kal HB, Struikmans H. Radiotherapy during pregnancy: Fact and fiction. Lancet Oncol 2005;6:328-33.  Back to cited text no. 65
    
66.
Loibl S, Schmidt A, Gentilini O, Kaufman B, Kuhl C, Denkert C, et al. Breast cancer diagnosed during pregnancy: Adapting recent advances in breast cancer care for pregnant patients. JAMA Oncol 2015;1:1145-53.  Back to cited text no. 66
    
67.
International Commission on Radiological Protection. Pregnancy and medical radiation. Ann ICRP 2000;30:iii-viii, 1-43.  Back to cited text no. 67
    
68.
Cardonick E, Gilmandyar D, Somer RA. Maternal and neonatal outcomes of dose-dense chemotherapy for breast cancer in pregnancy. Obstet Gynecol 2012;120:1267-72.  Back to cited text no. 68
    
69.
Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: An open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet 2015;385:1863-72.  Back to cited text no. 69
    
70.
Gadducci A, Cosio S, Fanucchi A, Nardini V, Roncella M, Conte PF, et al. Chemotherapy with epirubicin and paclitaxel for breast cancer during pregnancy: Case report and review of the literature. Anticancer Res 2003;23:5225-9.  Back to cited text no. 70
    
71.
Bines J, Earl H, Buzaid AC, Saad ED. Anthracyclines and taxanes in the neo/adjuvant treatment of breast cancer: Does the sequence matter? Ann Oncol 2014;25:1079-85.  Back to cited text no. 71
    
72.
Mir O, Berveiller P, Goffinet F, Treluyer JM, Serreau R, Goldwasser F, et al. Taxanes for breast cancer during pregnancy: A systematic review. Ann Oncol 2010;21:425-6.  Back to cited text no. 72
    
73.
von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): A randomised phase 2 trial. Lancet Oncol 2014;15:747-56.  Back to cited text no. 73
    
74.
Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, Stemmer SM, et al. Dose-dense chemotherapy in nonmetastatic breast cancer: A systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 2010;102:1845-54.  Back to cited text no. 74
    
75.
Moebus V, Jackisch C, Lueck HJ, du Bois A, Thomssen C, Kurbacher C, et al. Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: Mature results of an AGO phase III study. J Clin Oncol 2010;28:2874-80.  Back to cited text no. 75
    
76.
van Hasselt JG, van Calsteren K, Heyns L, Han S, Mhallem Gziri M, Schellens JH, et al. Optimizing anticancer drug treatment in pregnant cancer patients: Pharmacokinetic analysis of gestation-induced changes for doxorubicin, epirubicin, docetaxel and paclitaxel. Ann Oncol 2014;25:2059-65.  Back to cited text no. 76
    
77.
Zagouri F, Sergentanis TN, Chrysikos D, Papadimitriou CA, Dimopoulos MA, Bartsch R, et al. Trastuzumab administration during pregnancy: A systematic review and meta-analysis. Breast Cancer Res Treat 2013;137:349-57.  Back to cited text no. 77
    
78.
NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2; 2015. Available from: http://www.nccn.org. [Last accessed on 2018 Nov 20].  Back to cited text no. 78
    
79.
Amant F, Van Calsteren K, Halaska MJ, Gziri MM, Hui W, Lagae L, et al. Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: An observational study. Lancet Oncol 2012;13:256-64.  Back to cited text no. 79
    
80.
Pradat P, Robert-Gnansia E, Di Tanna GL, Rosano A, Lisi A, Mastroiacovo P, et al. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol 2003;67:968-70.  Back to cited text no. 80
    
81.
Cardonick E, Irfan F, Torres N. The use of Neupogen (filgrastim) or Neulasta (pegfilgrastim) during pregnancy when chemotherapy is indicated for maternal cancer treatment. J Cancer Ther 2012;3:157-61.  Back to cited text no. 81
    
82.
Sun C, Ding X, Wu Y, Yang L. Meta-analysis of associations between maternal breast cancer and the risk of adverse delivery outcomes. Int J Gynaecol Obstet 2018;140:146-52.  Back to cited text no. 82
    
83.
ACOG Committee on Obstetric Practice. ACOG committee opinion no 474: Nonobstetric surgery during pregnancy. Obstet Gynecol 2011;117:420-1.  Back to cited text no. 83
    
84.
Litton JK, Theriault RL, Gonzalez-Angulo AM. Breast cancer diagnosis during pregnancy. Womens Health (Lond) 2009;5:243-9.  Back to cited text no. 84
    
85.
Van Calsteren K, Heyns L, De Smet F, Van Eycken L, Gziri MM, Van Gemert W, et al. Cancer during pregnancy: An analysis of 215 patients emphasizing the obstetrical and the neonatal outcomes. J Clin Oncol 2010;28:683-9.  Back to cited text no. 85
    
86.
Lu D, Ludvigsson JF, Smedby KE, Fall K, Valdimarsdóttir U, Cnattingius S, et al. Maternal cancer during pregnancy and risks of stillbirth and infant mortality. J Clin Oncol 2017;35:1522-9.  Back to cited text no. 86
    
87.
Gziri MM, Hui W, Amant F, Van Calsteren K, Ottevanger N, Kapusta L, et al. Myocardial function in children after fetal chemotherapy exposure. A tissue Doppler and myocardial deformation imaging study. Eur J Pediatr 2013;172:163-70.  Back to cited text no. 87
    
88.
Cardonick E, Dougherty R, Grana G, Gilmandyar D, Ghaffar S, Usmani A, et al. Breast cancer during pregnancy: Maternal and fetal outcomes. Cancer J 2010;16:76-82.  Back to cited text no. 88
    
89.
Nugent P, O'Connell TX. Breast cancer and pregnancy. Arch Surg 1985;120:1221-4.  Back to cited text no. 89
    
90.
Alsaker MD, Opdahl S, Romundstad PR, Vatten LJ. Association of time since last birth, age at first birth and parity with breast cancer survival among parous women: A register-based study from Norway. Int J Cancer 2013;132:174-81.  Back to cited text no. 90
    
91.
Bladström A, Anderson H, Olsson H. Worse survival in breast cancer among women with recent childbirth: Results from a Swedish population-based register study. Clin Breast Cancer 2003;4:280-5.  Back to cited text no. 91
    
92.
Rodriguez AO, Chew H, Cress R, Xing G, McElvy S, Danielsen B, et al. Evidence of poorer survival in pregnancy-associated breast cancer. Obstet Gynecol 2008;112:71-8.  Back to cited text no. 92
    
93.
Johansson ALV, Andersson TM, Hsieh CC, Jirström K, Cnattingius S, Fredriksson I, et al. Tumor characteristics and prognosis in women with pregnancy-associated breast cancer. Int J Cancer 2018;142:1343-54.  Back to cited text no. 93
    
94.
Bonnier P, Romain S, Dilhuydy JM, Bonichon F, Julien JP, Charpin C, et al. Influence of pregnancy on the outcome of breast cancer: A case-control study. Societe Francaise de Senologie et de Pathologie Mammaire Study Group. Int J Cancer 1997;72:720-7.  Back to cited text no. 94
    



 
 
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