|Year : 2018 | Volume
| Issue : 2 | Page : 104-110
Pregnancy-associated breast cancer: An institutional experience
Samuel A Olatoke, Sulaiman O Agodirin, Adedire T Adenuga
Division of General Surgery, Department of Surgery, University of Ilorin Teaching Hospital, Ilorin, Kwara State, Nigeria
|Date of Web Publication||17-Jul-2019|
Dr. Samuel A Olatoke
Department of Surgery, University of Ilorin Teaching Hospital, Ilorin, Kwara State
Source of Support: None, Conflict of Interest: None
Introduction: Breast cancer is the second most common malignancy in pregnant women. Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy and the first postpartum year. PABC is associated with difficulty in detection, diagnosis, and definitive management. Management of these patients is centered on the wellbeing of both the fetus and the mother. We report the epidemiology, pathology, treatment, and outcome of patients with PABC managed at our institution. Patients and Methods: Twelve patients were managed for PABC by the Division of General Surgery from January 2012 to December 2017. Their records were retrieved and relevant information extracted. Results: Nine patients were diagnosed during pregnancy and three while lactating. All patients presented with stage III and IV disease, with all stage IV patients dying within 6 months of presentation. None of the children born to patients who had neoadjuvant chemotherapy had any obvious congenital anomaly at birth. Conclusion: The late stage at presentation of our patients means that antenatal screening of pregnant women for PABC should be strongly encouraged. Treatment of PABC in our setting should be aggressive and similar to that of nonpregnant patients. The use of taxane-based chemotherapy may improve outcome.
Keywords: Antenatal screening, breast cancer, chemotherapy, pregnancy
|How to cite this article:|
Olatoke SA, Agodirin SO, Adenuga AT. Pregnancy-associated breast cancer: An institutional experience. J Med Trop 2018;20:104-10
| Introduction|| |
Breast cancer is the most common cancer affecting women in Nigeria. It accounts for up to 50% of all cancer cases. Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within 1 year of delivery., It is the second most common malignancy in pregnant women and accounts for 3% of breast cancers in women worldwide., Nonetheless, it is not as rare as previously thought, as it is responsible for about 21% of all premenopausal breast cancer diagnosis found in women in Nigeria.
The management of PABC is not straightforward and can be challenging because of the difficulties associated with its diagnosis and treatment. The clinical manifestation may be obscured by the physiologic changes of pregnancy and lactation, and radiologic investigations might be misleading due to breast engorgement and density of the breast. Pathologic decisions may also be altered by the presence of rapidly dividing cells of the pregnant or lactating breast mimicking malignant features. The treatment of PABC is also hindered by conflict between fetal and maternal wellbeing.
Symptoms of PABC are often recognized later than their nonpregnant counterparts, and this may be adduced to the fact that many pregnant women interpret pathologic bodily changes as being physiologic. Although PABC is not a rare event, reports are scanty because of the challenges associated with the study population. Majority of the available reports are review articles and case reports. In this retrospective study, we report our experience with the management of PABC in a tertiary health center in Nigeria.
| Methods|| |
After due ethical considerations, records of patients diagnosed with breast cancer during pregnancy or within 1 year of delivery between January 2012 and December 2017 were identified in the registers of the Division of General Surgery of the hospital. Their records were retrieved from the records and pathology departments for data extraction. Data of interest were pattern of presentation (age, presenting complaint, duration of presenting complaint, parity, gestation age, and stage of disease), pathologic report (cytology, histology, and immunohistochemistry result), treatment modalities, and maternal and fetal outcome. Data was collected with the aid of specially designed proforma and analyzed using SPSS version 23 (IBM Corp., Armonk, NY). Demographic data were presented in descriptive statistics.
At the time of the study in our hospital, the routine was to initiate treatment for breast cancer after triple assessment that included clinical review, imaging with ultrasound, and fine-needle aspiration cytology or histology testing. Patients with features of advanced locoregional breast cancer were offered anthracycline-based neoadjuvant chemotherapy followed by simple mastectomy and axillary dissection. Immunohistochemistry reports were obtained from mastectomy specimen. The first-line regimen of chemotherapy was three weekly cycle of cyclophosphamide, epirubicin, and 5-fluorouracil.
| Results|| |
Pattern of presentation
Twelve patients were diagnosed with PABC during this period. The age ranged from 28 to 39 years (mean = 33 ± 3.4 years). The estimated fetal gestational age at diagnosis ranged from 16 to 36 weeks (mean = 24 ± 8.7 weeks). Nine patients were diagnosed during pregnancy, whereas three were diagnosed during lactation. The index pregnancy or lactation at diagnosis was the first in three of the patients, the second in three patients, the third in two patients, the fourth in two patients, the fifth in one patients, and the sixth in one patient [Figure 1]. Four patients were diagnosed at the third trimester of pregnancy, whereas five patients had their diagnosis at the second trimester [Figure 2]. The duration of symptoms ranged between 3 and 15 months (mean = 6 ± 3.8 months). The widest diameter of the breast masses ranged from 6 to 20 cm (mean = 11.6 ± 5.0 cm). There was axillary lymph node involvement in all, except a 32-year old patient who had angiosarcoma. Six patients had matted axillary nodes, and others were discrete. The presenting complaint was the presence of a breast lump in all patients. Only one patient was referred after positive screening from the antenatal clinic. The patients who were admitted from the emergency had severe anemia from bleeding breast ulcer, distant metastases (50%), and fungating breast disease (25%). Two patients were referred from the general outpatient department and were found to be pregnant after clinical evaluation.
|Figure 1: Index parity at diagnosis of PABC. PABC, pregnancy-associated breast cancer.|
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|Figure 2: Stage of the pregnancy at diagnosis of PABC. PABC, pregnancy-associated breast cancer.|
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Six of the patients presented with American Joint Committee on Cancer stage III whereas six presented with stage IV disease [Table 1].
All the patients had fine-needle aspiration cytology (FNAC) that was positive for malignant cells. Histologically, all the tumors, save one, were invasive ductal carcinoma. The exception was angiosarcoma. Immunohistochemistry results for the six patients who had mastectomies for invasive ductal cancer were triple negative.
Five of the patients with stage III disease had modified radical mastectomy and have been followed up for at least 9 months (range of follow-up = 9–52 months). Of the patients with stage III disease, three patients were in the second trimester, two in the third trimester close to term, and one diagnosed during lactation. Four patients had neoadjuvant chemotherapy with cytotoxic regimen consisting of 5-Fluorouracil, epirubicin and cyclophosphamide (FEC). Two patients did not receive neoadjuvant chemotherapy. The first was a 32-year-old patient with angiosarcoma. The second patient was a 31-year-old woman who presented at 34 weeks with a fast-growing tumor and had modified radical mastectomy was induced on the 36th week and adjuvant chemotherapy was commenced thereafter. The only woman from the metastatic group to have a mastectomy was a 28-year-old lady with an ulcerated bleeding right breast cancer with lung metastases. She had debridement mastectomy on account of torrential bleeding requiring multiple blood transfusions [Table 2].
All patient with stage IV disease had lung metastases, and two of them had concomitant pleural effusion that required closed thoracostomy tube drainage and chemical pleurodesis. A patient presented with both lung and multiple hepatic metastases [Table 3].
Maternal and fetal outcome
There were a total of eight deaths out of the 12 patients after 9 to 52 months of follow-up. All the patients with metastatic disease died within 6 months of presentation from progression of their disease. There were two deaths in patients who presented with stage III PABC. A 31-year-old woman developed intrauterine fetal death after the third course of neoadjuvant chemotherapy (FEC), subsequently expelled the fetus, developed sepsis postexpulsion, and died 3 days later. Another woman who had mastectomy for a stage III right breast angiosarcoma represented 6 months postoperative with features of local recurrence and distant metastases to the lungs. She died after 10 days of admission.
One patient presented with metastatic breast cancer at term. She had severe respiratory distress from bilateral lung parenchymal metastases and was on supplemental oxygen. After few hours of admission, she went into spontaneous labor and delivered a live male neonate with good APGAR scores. She died within an hour of delivery.
There were nine babies delivered, all via spontaneous vertex delivery: eight live babies and an intrauterine fetal death. The estimated fetal age at delivery was 37 weeks (35–38 weeks). None of the infants had any obvious congenital anomaly.
| Discussion|| |
PABC occurs in about one in 3000 patients; the mean age of 33 years in our center was in keeping with that of previous publications (32–34 years),, and is about a decade younger than the non-PABC group. Worldwide, the incidence of PABC is said to be increasing and is related to the increasing age at first pregnancy due to postponed childbearing. About 40% of Nigerian women would have their first child at 30-years of age and above. Every year of increase in the age of first delivery above 25 years leads to a 3.5% to 5% increase in lifetime breast cancer risk., It has been shown that the incidence rate of breast cancer jumps to a higher level during and just after each pregnancy and the protective effect of pregnancy on breast cancer is not seen till 10 to 15 years after. Nigerian women have an added risk of high parity with an average of four children per woman in the southwestern part of the country. The mean parity of our patients was 2.8 ± 1.6 that was not statistically different from the 3.4 ± 1.7 in other series reported for PABC cases and 4.1 ± 2.1 reported for non-PABC cases (P = 0.0898).
The most common presentation of PABC in our series was a painless mass. This is in keeping with the documented literature.,, The widest diameter of the breast masses range from 6 to 20 cm (mean 11.5 cm). This reflects a high tumor burden as reports in the western world state an average tumor diameter of 3 cm., None of our patients presented in stage I or stage II; 50% of our patients presented with stage IV that is about six times the 9% quoted in western literature. This is similar to reports that show that even non-PABC presentation is usually at advanced stages in up to 75% of Nigerian patients.,,
A diagnostic delay of 2 to 15 months is noted in our patients with PABC, with a mean delay of about 6 months. This diagnostic delay is about 1 month longer than the average of 5 months quoted in many studies., A delay in diagnosis increases the risk of lymph node involvement by up to 1.8% with every month delay; 45% of patients had matted axillary lymph nodes at presentation. Again, this is typical of the aggressive nature of PABC, as these tumors tend to have with early lymph node involvement and spread.
The delay in presentation is usually due to the mass being attributed to normal breast physiologic changes. Despite the difficulty in diagnosis of PABC, due to the effects of pregnancy on the breast, several investigative modalities with high specificity and sensitivity are available to aid the diagnosis. Each should be interpreted with care and the presence of false positives and negatives should be entertained if investigative findings are incongruent with the clinical outlook. Breast masses may be masked on mammography due to engorgement and increased density of the breast; even though the amount of radiation exposure to mammography is small and inconsequential, many workers believe ultrasound is the preferred radiological modality of choice especially in the first trimester.,,
Termination of pregnancy was a routine protocol in the management of PABC for about 2 decades ago. Reasons adduced are that the continuous hormonal milieu of the pregnant state encouraged rapid growth of the tumor and aborting the embryo/fetus may slow the progression of the disease. Recent studies have debunked this. There has been no difference in outcome in patients who have had termination of pregnancy on account of PABC and their counterparts who did not have termination of pregnancy and is therefore strongly discouraged for such purposes., If maternal outcomes are not negatively impacted by the pregnancy itself, continuation of pregnancy seems not only reasonable but also recommended. Nevertheless, in cases of advanced disease stage (stage III or IV) or for high-grade or aggressive primary tumors diagnosed in the early first trimester, termination of pregnancy may be considered (on account of teratogenic risk of chemotherapy during the first trimester). None of our patients had a voluntary termination of pregnancy. They all presented in the second and third trimester of pregnancy and were managed as such.
Treatment was selected according to best practice. Literature has suggested that the chemotherapeutic regimen of choice in PABC is adriamycin-based chemotherapy and this regimen has be adjudged to be safe in pregnancy. All patients who had chemotherapy received a standard dose of 500 mg/m2of cyclophosphamide, epirubicin at a dose of 50 mg/m2, and 500 mg/m2of 5-fluorouracil in three weekly cycles. No grade 3 to 5 toxicities were seen in patients who had this regimen. Even in the setting of metastasis and the presence of a high burden of locally advanced tumor and fungation, this regimen was maintained. There was no documentation of a switch to taxane or platinum-based chemotherapy regimen despite the aggressive and advanced stages of the presentation of the patients. The fear of fetal toxicity as well as the astronomical cost of taxanes were the likely reasons.
Advances in treatment in nonpregnant patients are slow to be adopted in the treatment protocols for pregnant women. Pregnant women should be offered the same life-saving treatment, expecting the same response to treatment. Taxanes improve both disease-free survival and overall survival in breast cancer patients and are widely used as standard first-line treatment of high-risk, early-stage, and advanced/metastatic breast cancer in nonpregnant women, resulting in a better response rate and longer time to progression than standard anthracycline-based regimens. Emerging studies in pregnant women have shown good clinical response with toxic effects no more than the anthracycline-based ones., As all our patients presented with advanced/metastatic disease, it is suggested that first-line chemotherapy for PABC patients in this environment should be taxane therapy. Aggressive management is needed to improve survival as the mortality of 67% recorded is higher than what obtains in developed climes.
Surgery is the only modality that can ensure cure. Six mastectomies were done. Five stage III patients had modified radical mastectomy and one patient with stage IV disease had a debridement mastectomy for a bleeding breast ulcer. Generally, radiotherapy is given after delivery as it is associated with a high rate of teratogenesis and abortions when given at the first trimester, and also hematological problems in the newborn when given close to term. Hormonal treatment of PABC is contraindicated. Tamoxifen is associated with Goldenhar syndrome and ambiguous genitalia.
Histology of five out of six mastectomy specimens yielded invasive ductal cancer that was similar to the findings of Middleton et al. All but one of our patients had invasive ductal carcinoma that is the most common subtype of breast cancer. Our result somewhat differs from Sule and Ewemade who reported 33% incidence in his series of patients with PABC. We had a 32-year-old woman with primary angiosarcoma of the breast. She represented 6 months after mastectomy with evidence of local recurrence and lung metastases. Angiosarcomas are rare, respond poorly to chemotherapy and radiotherapy, and have a poor prognosis.,Immunohistochemistry of all nonsarcoma mastectomy specimens showed triple negative results. This high rate of triple negativity is typical of PABC and is partly responsible for the poor prognostic outcome.,
The mortality rate in this series was about 67% that is about three times the mortality rate reported by 23% reported by García-Manero et al. in Europe and almost twice the 39% mortality rate quoted for non-PABC patients here in Nigeria.
The recommendations are as follows: comprehensive breast examination during antenatal visits and prompt referral of patients with suspicious breast examination findings to a specialist; multidisciplinary team (including obstetrics and neonatology) to manage PABC patients; and aggressive treatment as similar as possible to a nonpregnant patient with early use of taxanes as first line and also including chemotherapy drugs to list of drugs covered by insurance to improve affordability.
| Conclusion|| |
PABC carries a poor prognosis, and the limitations of management notwithstanding. No woman should lose her life while trying to create life. Management should be tailored to the patient. Factors such as stage of the disease, trimester stage, and fetal outcome should be paramount in every management protocol. Early detection is key in the management of PABC, as it is associated with better outcomes.
There is a role for health professionals who care for pregnant women in the early diagnosis of PABC. The importance of antenatal breast examination as a means of screening should be encouraged. Midwives should be trained on how to examine the breast and refer to a breast surgeon after detection of a suspicious lump in a pregnant woman’s breast.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]