Purpose: The objective of this study is to analyze our case series of pregnancy associated breast cancer (PABC) and compare it with what is reported in the international literature.

Material and methods: retrospective study carried out in patients with breast cancer who are pregnant or in the postpartum period, up to one year after the delivery in the period between January 2009 up to December 2022. All patients had histologically confirmed invasive breast tumors, with immunohistochemical analysis performed by the Department of Pathology at the Hospital Alemán. Variables were evaluated, including presentation, stage at diagnosis, treatment received, and gestational age reached.

Results: A total of 16 patients with PABC were included, representing 1% of all breast cancer cases at Hospital Alemán. Of these, 62.5% (n=10) during pregnancy whereas the other 37.5% (n=6) were diagnosed in the postpartum period. The most common clinical presentation was a palpable lump, observed in 81.2% (n=13) patients. Stage II was the most frequently diagnosed, representing 68.8% (n=11) of the cases, and 37.5% (n=6) were triple negative subtypes. None of the pregnant women (10/16) terminated their pregnancy. The average gestation time was 35 weeks. Out of all patients, 9 underwent mastectomy and 6 received breast-conserving surgery. The remaining case presented with metastasis at diagnosis. Of the 10 patients diagnosed during pregnancy, 5 (50%) received neoadjuvant chemotherapy, while the remaining 5 (50%) underwent primary surgery.

Conclusion: This retrospective study allows us to document that, despite the small number of patients evaluated, the results are comparable to those reported in the international literature. The association between breast cancer and pregnancy adds complexity to oncologic treatment planning, as many therapies may pose potential risks to the fetus. The management of this association requires a multidisciplinary approach.

Keywords: breast cancer, pregnancy

Breast cancer (BC) is the most frequently diagnosed oncological pathology, and the main cause of cancer death in women.¹ BC is the cancer most frequently diagnosed during pregnancy, occurring in 1 to 4 cases per 10,000 pregnancies.^2,3

PABC is considered to be diagnosed from fertilization or up to one year post partum. However, this definition has recently been questioned.⁴ Physiological changes during pregnancy and underestimation of symptoms by health professionals can delay diagnosis.⁵ This implies its recognition in more advanced stages compared to non-pregnant women.⁶

About 10% of BC occur in patients under 40 years of age and between 0.2% to 2.6% of all breast cancers occur during pregnancy.⁷

During pregnancy, the most frequently diagnosed BC phenotypes are those of greater aggressiveness, as in young patients. In turn, pregnant patients have a higher incidence of more advanced stages when compared to the general population.⁷

Estrogen receptor (ER)-positive tumors are less common in younger women and are found at even lower rates in women with PABC compared to age-matched controls.^8–10 On the contrary, HER2-positive tumors are relatively more common in pregnant patients, which could contribute to a worse prognosis. However, both overall survival (OS) and disease-free survival (DFS) are similar when compared to non-pregnant breast cancer patients adjusted for age at diagnosis, stage, histological tumor type, the immunohistochemical phenotype and the treatment performed.^8–10

Pregnancy adds complexity to cancer treatment planning, as many therapies can be potentially dangerous to the fetus. It is important to note that termination of pregnancy has not demonstrated benefits in regards to the prognosis of the disease, and this should be explained carefully to the patient to aid decision-making.¹⁰

Taking into account the gestational age, we can say that the therapeutic protocols for BC during pregnancy are the same as those for non-pregnant women and are based on the stage of the disease.⁵

Recent publications compare perinatal data between pregnant women with and without neoplasms. PABC had a higher risk of preterm birth, lower birth weight, and neonatal mortality.¹¹

Type of study

Observational, retrospective and descriptive study.

Inclusion Criteria – Population under study

1. Pregnant or postpartum breast cancer patients, up to one year post partum.
2. Evaluated and treated at our institution.
3. Patients in the period from January 2009 to December 2022.
4. Invasive breast tumor documented histologically and with an immunohistochemical study carried out.
5. The variables evaluated are described below:

1. Year of diagnosis
2. Age at diagnosis
3. Time of diagnosis
4. Form of presentation
5. Stage
6. Immunohistochemical phenotype
7. Treatment performed during pregnancy h.​ Genetic study
8. Interruption of pregnancy
9. Gestational age at the time of delivery.

Statistical treatment

The results were analyzed by statistical programs for a descriptive analysis.

During the period from January 2009 to December 2022, 1,469 cases of BC were treated, of which 533 were diagnosed in those under 45 years of age and 247 in those under 40 years of age. 16 patients were diagnosed with PABC, which represented 1% of the total cases, 3% among those under 45 years of age and 6.5% among those under 40 years of age. The average age at the time of diagnosis was 34 years (range 25-39 years). 37.5% of the patients (n=6) were diagnosed during the postpartum period and the remaining 62.5% (n=10) during pregnancy. In this last group, 2 (20%) were diagnosed in the first trimester, 6 (60%) during the second trimester and 2 (20%) during the third trimester.

The most frequent clinical manifestation was a palpable nodule in 13 patients (81.2%), in 2 patients (12.5%) the diagnosis corresponded to ultrasound imaging and in the remaining patient (6.2%) the diagnosis was made by retraction in the breast skin. Grouped by stages according to the classification of the American Joint Committee on Cancer (AJCC-TNM) 11, we found 3 stages I (18.8%), 11 stages II (68.8%), 1 stage III (6.3%) and 1 stage IV (6.3%).

Regarding the immunohistochemical phenotype, 4 patients had luminal A type tumors (25%), 2 patients had luminal B type tumors (12.5%), another 4 patients had HER2 + type tumors (25%) and the remaining 6 had tumors triple negative type (37.5%). The Ki-67 average was 44%.

Out of all patients, 9 underwent mastectomy and 6 received breast-conserving surgery. The remaining case presented with metastasis at diagnosis. Of the 10 patients diagnosed during pregnancy, 5 (50%) underwent neoadjuvant chemotherapy treatment, the remaining 5 (50%) underwent initial surgery, of which 2 (40%) underwent conservative treatment and 3 (60%) mastectomy. No patient received radiotherapy, endocrine therapy or anti-HER treatment during pregnancy.

All patients received genetic counseling, of which 7 (43.7%) women underwent a genetic study, of which 5 (71.4%) had no evident alteration and 2 (28.6%) were BRCA mutated. These two patients underwent a bilateral mastectomy.

None of the pregnant women (10/16) terminated their pregnancy. It was documented that 5 of the 10 pregnant women were able to achieve a full-term pregnancy. The average gestation was 35 weeks.

With an average follow-up of 5 years, three recurrences and one death due to the underlying disease were observed.

In the group studied, rates similar to those reported in the international literature can be observed.⁴ The rate of BC in those under 40 years of age reported is similar to that observed (1-3% vs 1%).⁵ One data to study is the 6.5% of PABC, found in our study, which is higher than the 3% described in the literature.¹⁰ The average age is similar to that reported by the literature, being 34 years vs. 36 years.⁷ Both the most frequent form of presentation (palpable nodule) and the distribution by stages were consistent with the published literature.⁵

The distribution according to the immunohistochemical type and the Ki67 rate in our work was similar to that reported in the literature.^2,7 According to the literature consulted, women carrying mutations in the BRCA genes do not have an increased risk of PABC. In the two cases with mutations we underwent bilateral mastectomy.

Regarding pregnancy outcomes, no adverse effects were observed in the newborns of the 5 patients who underwent neoadjuvant chemotherapy. The regimens used in these 5 patients included doxorubicin and cyclophosphamide, which can be used during pregnancy.¹²

This retrospective study allows us to document that, despite the low number of patients evaluated, the results are comparable to those published in the international literature. This is also the case with regard to distribution according to stage and immunohistochemical phenotype.

Systematic genetic evaluation of patients with PABC is mandatory, as it provides valuable information to guide the proposed treatment.

The association of BC and pregnancy adds complexity to oncological treatment planning, since many therapies can be potentially dangerous for the fetus.

The approach to PABC should be multidisciplinary, placing particular interest in the evaluation and strict monitoring of the breast in all pregnant women.

All of this stimulates us to continue our research in order to confirm or rectify the percentage trends observed.

None.

None.

The authors declares that there is no conflict of interest.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin. 2021;71(3):209–249.
2. Salani R, Billingsley CC, Crafton SM. Cancer and pregnancy: An overview for obstetricians and gynecologists. Am J Obstet Gynecol. 2014;211(1):7–14.
3. Parazzini F, Franchi M, Tavani A, et al. Frequency of pregnancy related cancer: A population based linkage study in Lombardy, Italy. Int J Gynecol Cancer. 2017;27(3):613–619.
4. Amant F, Lefrère H, Borges VF, et al. The definition of pregnancy–associated breast cancer is outdated and should no longer be used. Lancet Oncol. 2021;22(6):753–754.
5. Amant F, Loibl S, Neven P, et al. Breast cancer in pregnancy. Lancet. 2012;379(9815):570–579.
6. Ulery M, Carter L, McFarlin BL, et al. Pregnancy–associated breast cancer: Significance of early detection. J Midwifery Women’s Health. 2009;54(5):357–363.
7. Boere I, Lok C, Poortmans P, et al. Breast cancer during pregnancy: epidemiology, phenotypes, presentation during pregnancy and therapeutic modalities. Best Pract Res Clin Obstet Gynaecol. 2022;82:46–59.
8. Aziz S, Pervez S, Khan S, et al. Case control study of novel prognostic markers and disease outcome in pregnancy/lactation–associated breast carcinoma. Pathol Res Pract. 2003;199(1):15–21.
9. Bonilla L, Ben–Aharon I, Vidal L, 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(24):1845–1854.
10. Amant F, von Minckwitz G, Han SN, et al. Prognosis of women with primary breast cancer diagnosed during pregnancy: Results from an international collaborative study. J Clin Oncol. 2013;31(20):2532–2539.
11. Lu D, Ludvigsson JF, Smedby KE, et al. Maternal cancer during pregnancy and risks of stillbirth and infant mortality. J Clin Oncol. 2017;35(14):1522–1529.
12. 8ª edición de la Clasificación TNM. American Joint Committee on Cancer (AJCC–TNM); 2017.