Considerations for Maternal and Child Well-being
Detectingcancer in pregnant individuals presents the multifaceted challenges, necessitating a comprehensive approach to balance curative treatment for the patient while safeguarding the well-being of the fetus. Although breast cancer has been recognized since ancient times, its incidence remained relatively low before 18th century, owing to advancements in sanitation and disease administration that extended human lifespan significantly. The first documented case of breast cancer occurring during pregnancy dates back to 1869. Pregnancy-associated breast cancer encompasses cases diagnosed either during pregnancy or within a year post-delivery. Its stands as the second most prevalent cause of death among women within the reproductive age rang.Yet ,occurrences during pregnancy and lactation are infrequent accompanied by an approximate frequency of one case per 1000 pregnancies. Timely diagnosis has been shown to increase breast cancer survival rates by 50%. Notably women who have experienced their initial full-term pregnancy/ birth (FFTB) prior to the age of 20, there is a 50% reduction in the life time risk of breast cancer occurrence in contrast to the nulliparous women.
Conversely, first births after the age of 35 are associated with an elevated risk of breast cancer development. Breast cancer, cervical cancer, lymphoma, ovarian cancer, leukemia, colorectal cancer and melanoma are among the utmost frequently diagnosed cancers during pregnancy. Given the youthful Patient’s age afflicted with breast cancer during pregnancy, it is imperative to provide comprehensive genetic counseling services. Breast cancer during pregnancy is marked by a lower prevalence of hormone receptor expression, resulting in a predominance of aggressive subtypes such as triple-negative or HER2-positive, which are commonly observed in younger individuals. Diagnosis typically occurs at advanced stages compared to non -pregnant patients, potentially worsening prognosis due to delayed diagnosis, challenges in staging due to imaging risks, and suboptimal management.
Genome-wide assessments of copy number alterations in primary tumor samples revealed no significant differences between patients and controls. Comprehensive examination through whole genome sequencing has unveiled notable disparities in pregnancy associated breast cancer. Specifically, there is a marked increase in missense mutations as well as alterations within the mucin gene family. Moreover, an enhancement of the mutational signature associated with mismatch repair deficiency is observed, along with elevated levels of stromal and tumor- infiltering lymphocytes (TILs). Hinting at a plausible influence of pregnancy on tumor biology Certain risk factors for breast cancer during pregnancy remain unclear, as they share similarities with the genetic and environmental factors associated with breast cancer adjusted for age in the general population. Individuals with BRCA1 with BRCA2 mutation are not at increased risk during pregnancy. Common indicators of breast cancer during pregnancy includes the presence of lump or mass in the breast tissue in addition possible nipple discharge, alterations in nipple or breast skin appearance, and breast pain.
Clinicians can confidently utilize ultrasound, mammography, biopsy, computed tomography (CT) ,and MRI as diagnostic modalities to rule out the presence of breast carcinoma .In case of breast cancer diagnosed during pregnancy, therapeutic intervention are available to address both maternal and fetal health. Typically, surgical interventions is prioritized as the initial therapeutic measure, followed by adjuvant chemotherapy and/or radiotherapy. Close surveillance throughout the gestational period is essential to prevent metastasis. With appropriate medical management, numerous affected women achieve successful pregnancies and deliver healthy infant.
Factors contributing to risk for pregnancy-associated breast cancer (PABC) exhibit parallels to those observed in age-matched breast cancer cohorts. Individuals harboring mutations in BRCA1 or BRCA2 genes are particularly prone to early-onset breast malignancies, with hormonal changes during pregnancy potentially exacerbating this susceptibility. Figure 1 illustrate an algorithm delineating the treatment of patients with pregnancy-associated breast cancer (PABC). Due to physiological shifts during pregnancy, PABC typically presents as a painless. Diagnosis usually begins with breast ultrasonography, known for its safety and high sensitivity and specificity.
Upon encountering a suspicious mass indicative of PABC obtaining a histopathological diagnosis, serving as the gold standard. While the histological characteristics of PABC typically resemble those found in non-pregnant individuals of similar age, informing the pathologist of the patient’s pregnancy status is essential. Invasive ductal carcinoma is the predominates, comprising around 80-90% of PABC cases. Cases of pregnancy-associated breast cancer (PABC) frequently show a greater prevalence of hormone receptor (HR) negativity, HER2 positivity, and increased Ki67 levels (defined as >14%) compared to breast cancer in young non-pregnant individuals. This results in a lower occurrence of the luminal A subtype and a higher frequency of triple-negative and HER2-overexpressing breast cancer subtypes among patients with(PABC).
Following the confirmation of a malignancy, pathologically it is recommended to undergo bilateral mammography to evaluate for bilateral and multi centric disease). Mammography is considered safe for the fetus with radiation dose well below established safety threshholds. Hence, It is recommended to avoid using contrast-enhanced breast magnetic resonance imaging (MRI) in patients diagnosed with Pregnancy-Associated Breast Cancer (PABC), reserving its use solely for advanced stages where it might influence clinical interventions. A approved contrast agents such as gadobenate dimeglumine and gadoterate meglumine should be used if MRI is necessary.
Radiographic staging assessments should generally be avoided during pregnancy, except in cases where there is a high risk of metastatic disease, and outcomes have the potential to influence clinical decision-making. An interdisciplinary team comprising radiologists and nuclear medicine physicians should collaborate to devise strategies to assess and mitigate cumulative fetal radiation exposure. Common imaging modalities employed for metastatic investigations and staging in (PABC) include chest X-ray, liver ultrasound, and non-contrast bone MRI, all considered safe for fetal exposure. Non-contrast MRI is the favored approach for diagnosing bone metastases; however, bone scintigraphy becomes an option in cases where MRI outcomes are inconclusive or when MRI is not available. PET scans are not recommended for staging in PABC patients.
