Pregnancy-Associated Breast Cancer: From Clinical and Treatment Challenges to the Emerging Role of Artificial Intelligence

1. Introduction

Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or in the first postpartum year, with a frequency commonly cited as approximately 1 in 3,000 pregnant women [1].

Contemporary population-based estimates vary by definition and denominator: a Swedish registry cohort (1963–2002) reported that incidence increased from 16.0 to 37.4 per 100,000 deliveries, [2] while a U.S. population-based cohort (1999–2008) found an overall 10-year incidence of 6.5 cases per 100,000 births [2,3].

A 2025 systematic review/meta-analysis estimated that the global incidence of PABC amounts to 19.2 cases per 100,000 pregnancies and has been increasing slowly, [4] and a regional linkage study in Lombardy (2001–2012) reported breast cancer at 39.9 per 100,000 pregnancies and noted no trend with calendar year [4,5].

Temporal variations are likely influenced by demographic and epidemiological changes. In the United States, researchers observed that as the age of first pregnancy increases, the incidence of breast cancer diagnoses during pregnancy also escalates, while population surveillance indicates a more pronounced rise in breast cancer incidence among women under 50 years, at an annual rate of 1.4%) [7].

Clinically, PABC poses significant challenges as diagnosis is often delayed due to pregnancy-related physiological alterations that can obscure breast masses. Additionally, imaging efficacy is compromised since mammography is relatively less effective during pregnancy and lactation, with heightened mammographic density diminishing sensitivity [8,9].

Management is further limited by treatment safety that varies by trimester; expert opinion is that chemotherapy is inappropriate during the first trimester of pregnancy but may be administered in the second and third trimesters [10].

From a surgical oncology standpoint, these circumstances highlight the necessity for immediate, pregnancy-specific diagnostic protocols and early interdisciplinary collaboration to ensure fast locoregional control while preserving fetal health. This narrative review consolidates existing knowledge about the incidence, diagnostic methodologies, and trimester-specific multidisciplinary care of PABC, highlighting practical decision-making considerations for general oncologic surgeons.

2. Materials and Methods

This study was conducted as a narrative review summarizing the current evidence on the diagnosis, multidisciplinary management and treatment of pregnancy-associated breast cancer (PABC). Particular emphasis was placed on clinically relevant aspects including epidemiology, diagnostic strategies, surgical treatment, systemic oncologic therapy, obstetrical management and emerging technologies such as artificial intelligence in clinical decision-making.

A comprehensive literature search was performed in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify relevant publications on breast cancer during pregnancy. Articles published between 2000 and 2025 were considered, with priority given to studies from the last decade.

Search terms included combinations of the following keywords and MeSH terms: “pregnancy-associated breast cancer”, “breast cancer during pregnancy”, “breast neoplasms AND pregnancy”, “chemotherapy during pregnancy”, “breast surgery during pregnancy”, “oncologic management pregnancy”, “artificial intelligence breast cancer”.

Eligible publications included original research articles, systematic reviews, meta-analyses, clinical guidelines and consensus statements focusing on the diagnosis, treatment or outcomes of pregnancy-associated breast cancer. Only peer-reviewed articles published in English were included.

Studies were screened based on title, abstract and full-text evaluation, relevant data regarding epidemiology, diagnostic methods, treatment strategies, and maternal-fetal outcomes were being extracted.

Due to the narrative design of the review, the findings were synthesized qualitatively rather than through meta-analysis. Evidence was organized into thematic sections addressing key aspects of PABC management, prioritizing recent studies, international guidelines and large observational cohorts.

3. Clinical and Therapeutic Aspects of Pregnancy-Associated Breast Cancer

3.1. Risk Factors

The information regarding PABC risk factors encompasses many study methods (case-control, registry cohorts, and narrative reviews), and multiple sources expressly indicate that PABC-specific risk factors are not fully defined [4].

Maternal age and reproductive time consistently appear as significant variables throughout the available data. A later age at first pregnancy or childbirth is consistently recognized as significant for the risk and occurrence of PABC, whereas registry comparisons reveal that reproductive timing characteristics distinguish between pregnancy-associated and non-pregnancy-associated cases [4,11].

A nationwide breast cancer registry analysis revealed that factors more strongly associated with PABC compared to non-PABC included advanced maternal age at first childbirth (≥30 years) and overweight status (BMI ≥23 kg/m²), thereby reinforcing the notion that PABC cases tend to cluster among individuals exhibiting both delayed childbearing and increased adiposity [11,12].

Hereditary predisposition is notably significant as numerous PABC cases arise in younger women; a clinical evaluation indicates that BRCA mutations are disproportionately prevalent in this age range, offering strong implications for therapeutic management [1,13].

Evidence from population-based case–control studies indicates that family history and BRCA status may have a greater impact in the immediate postpartum subset compared to other premenopausal breast cancers, aligning with a "high-risk subgroup" model rather than a uniform profile for postpartum breast cancer risk [14,15,16].

During the postpartum period, pregnancy-related exposures may be significant: a countrywide health insurance study A database analysis identified advanced mother age (≥35 years) and cesarean birth as risk factors for postpartum breast cancer, but primiparity correlated with a reduced risk [17].

In addition to epidemiologic associations, the biology of pregnancy and lactation is frequently suggested as a contributing factor: reviews emphasize hormonal alterations, temporary immunosuppression, and post-lactation involution/proinflammatory remodeling as potential mechanisms that may heighten susceptibility or expedite the proliferation of pre-existing transformed cells [18,19].

Numerous established breast cancer risk factors are potentially pertinent to pregnancy-associated diagnoses, including previous chest radiation exposure and elevated mammographic breast density, which are recognized indicators of breast cancer risk in general populations [20,21].

3.2. Clinical Presentation

PABC generally manifests with localized breast symptoms, predominantly as a painless palpable lump [22].

In cohort and institutional studies, a palpable mass constitutes the primary mode of presentation (approximately 90%), whereas additional symptoms—such as nipple discharge, focal pain, diffuse breast enlargement, skin thickening or inflammatory changes, and axillary issues—may coexist with the mass and are more prevalent in PABC compared to non-pregnancy-associated cases [23].

In lactating patients, "milk rejection" (infant unwillingness to nurse) is an acknowledged, albeit rare, presenting symptom [23].

Clinical identification is hindered by physiological breast alterations associated with pregnancy and lactation. During these intervals, breast evaluation is impeded by enlargement, tenderness, heightened nodularity, and hormonally induced ductal and lobular proliferation, which can enhance firmness and hide localized disease [24].

Simultaneously, prevalent benign entities (e.g., lactational adenoma) and inflammatory states may resemble malignancy, necessitating increased clinical vigilance to distinguish benign from malignant disease [25].

Consequently, any novel or developing breast abnormality during pregnancy or the early postpartum period should be regarded as potentially malignant until proven otherwise; notably, an open-access review underscores that due to the increased glandular nodularity associated with pregnancy, a mass persisting beyond 2–4 weeks should elicit suspicion and necessitate imaging or biopsy rather than mere reassurance or postponement [8].

3.3. Clinical Diagnostic

The limits of the aforementioned examination highlight the necessity for systematic evaluation in response to clinical findings, rather than just reassurance, as diagnostic imaging and biopsy decisions originate from bedside assessment [23,24].

Biopsy is necessary for the diagnosis of tissue in cases of worrisome palpable findings [26,27,28].

During biopsy procedures, one must anticipate certain difficulties in histologic and cytologic interpretations connected to pregnancy. A thorough study specifically recommends that pathologists be informed when doing a core biopsy, as pregnancy elevates the cellularity of breast tissue [29].

3.4. Imagistic Diagnostic

In cases of suspected PABC, there is a consensus that breast and axillary ultrasound is the primary diagnostic technique, as it facilitates swift identification of palpable abnormalities and targeted assessment of axillary nodal status without the use of ionizing radiation [28].

The American College of Radiology acknowledges that mammography is safe during pregnancy and that diagnostic breast imaging should be performed when clinically warranted, especially for locoregional staging of newly diagnosed PABC [23].

Mammography conducted during pregnancy necessitates dose minimization, sometimes employing abdominal shielding, with the fetal dose deemed negligible when executed correctly [28].

Mammography retains clinical significance as it can reveal microcalcifications, asymmetry, architectural distortion, and skin thickening, even in dense parenchyma. It is emphasized as a complement to ultrasound, as it may identify otherwise hidden malignant microcalcifications that influence local staging, such as the extent of DCIS [28,30].

The American College of Obstetricians and Gynecologists asserts that ultrasonography and MRI have no related risks but should be employed judiciously for clinically pertinent inquiries [30].

Gadolinium exposure is a significant concern: a substantial population-based investigation indicated correlations between gadolinium-enhanced MRI during pregnancy and negative outcomes, including stillbirth or neonatal mortality [31].

The European Society for Medical Oncology's statement on pregnancy-related breast cancer advises against the use of dynamic contrast-enhanced (DCE) breast MRI and highlights that diffusion-weighted imaging allows for non-contrast breast MRI in specific instances [10].

Systemic staging pertains to imaging that assesses distant metastatic disease (M in TNM). In nonpregnant patients, especially those with advanced disease, whole-body staging typically employs a combination of CT and bone scintigraphy and/or PET-CT. Contemporary reviews highlight PET-CT as a sensitive method for identifying metastases in advanced breast cancer, with TNM classification explicitly directing staging decisions [32].

During pregnancy, staging is tailored to risk rather than being standardized. The European Society for Medical Oncology consensus asserts that locoregional tumor stage dictates the staging approach during pregnancy, advocating for chest X-ray and abdominal ultrasound as readily available first-line screening modalities for metastases, and recommending escalation to non-contrast MRI with diffusion-weighted sequences (spine/pelvis and liver) and low-dose chest CT when suspicion is elevated or findings are ambiguous [10].

The consensus advocates for whole-body diffusion-weighted MRI as a singular systemic staging method, highlighting its capacity to enhance nodal and distant metastatic staging without the need of ionizing radiation [10].

Ultimately, PET-CT and bone scintigraphy are explicitly considered: while nuclear tracers may result in relatively minimal fetal exposure, the incorporation of CT in hybrid imaging elevates the cumulative dose; thus, low-dose PET-CT and bone scintigraphy are categorized as second-line options, employed selectively when findings remain unresolved and the maternal benefit distinctly surpasses the fetal risk, with discussions regarding fetal cumulative exposure limits [10,33].

Due to the alterations in intent and sequencing caused by systemic staging findings (M1), a pregnancy-adapted staging pathway must be explicitly associated with decisions on upfront surgery versus neoadjuvant systemic therapy and the axillary strategy, particularly when radiotherapy is postponed [10].

Table 1. Safety and Clinical Use in Systemic Staging Imaging in PABC.

Modality	Pregnancy Use	Rationale	Reference
Chest X-ray (+shield)	Use (baseline)	Low fetal dose (≪1 mGy); recommended as baseline screen.	[34]
Abdominal US	Use (baseline)	No radiation; recommended for liver nodal survey.	[30]
WB MRI (no contrast)	Use/conditional	No radiation; high sensitivity for marrow/viscera; whole-body DWI-MRI is proposed as ideal staging modality.	[10]
Low-dose CT (thorax/abd)	Conditional	Limited fetal dose with shielding; used if MRI unavailable (guidelines suggest CT/US first).	[10]
PET-CT (FDG)	Avoid/second-line	Higher fetal dose; only if other imaging inconclusive and high suspicion.	[10]
Bone Scintigraphy	Avoid/second-line	Fetal radiation (from Tc-99m); only if urgent need to detect bone mets (rare).	[33]

Table 1. Safety and Clinical Use in Systemic Staging Imaging in PABC.

Modality	Pregnancy Use	Rationale	Reference
Chest X-ray (+shield)	Use (baseline)	Low fetal dose (≪1 mGy); recommended as baseline screen.	[34]
Abdominal US	Use (baseline)	No radiation; recommended for liver nodal survey.	[30]
WB MRI (no contrast)	Use/conditional	No radiation; high sensitivity for marrow/viscera; whole-body DWI-MRI is proposed as ideal staging modality.	[10]
Low-dose CT (thorax/abd)	Conditional	Limited fetal dose with shielding; used if MRI unavailable (guidelines suggest CT/US first).	[10]
PET-CT (FDG)	Avoid/second-line	Higher fetal dose; only if other imaging inconclusive and high suspicion.	[10]
Bone Scintigraphy	Avoid/second-line	Fetal radiation (from Tc-99m); only if urgent need to detect bone mets (rare).	[33]

3.5. Surgery During Pregnancy

Breast surgery is a fundamental treatment for PABC. In contrast to various systemic medications, surgical intervention can typically be conducted safely during pregnancy, contingent upon adherence to suitable obstetric, anesthetic, and oncologic precautions. Current international standards assert that surgery should not be deferred purely due to pregnancy when oncological reasons are present, as delaying final treatment may negatively impact maternal prognosis [10,35]. A multidisciplinary strategy that includes breast surgeons, anesthesiologists, obstetricians, neonatologists, and medical oncologists is crucial for optimizing mother and fetal outcomes [9,35].

Multiple cohort studies have shown that non-obstetric oncologic surgery during pregnancy does not correlate with a heightened risk of congenital abnormalities, especially when contemporary anesthetic methods and suitable maternal-fetal monitoring are implemented [29,35].

Modern anesthetic techniques allow safe surgical procedures during pregnancy, although careful maternal and fetal monitoring is required. Key recommendations include:

• Left lateral tilt positioning to prevent inferior vena cava compression
• Continuous maternal oxygenation monitoring
• Maintenance of uteroplacental perfusion
• Avoidance of maternal hypotension

Mastectomy and breast-conserving surgery (BCS) are deemed viable surgical choices for pregnant patients, contingent upon tumor features, gestational age, and expected adjuvant therapy. Historically, mastectomy was more commonly conducted as adjuvant radiation typically had to be deferred until post-delivery. Contemporary research indicates that breast-conserving surgery (BCS) can be safely conducted when radiation is postponed until the postpartum phase, without jeopardizing oncologic outcomes [9].

Precise axillary staging is crucial in the treatment of PABC. Sentinel lymph node biopsy (SLNB) with technetium-99m radiocolloid has demonstrated safety and reliability during pregnancy, with negligible fetal radiation exposure [36]. Methylene blue dye is prohibited due to possible teratogenic effects and the danger of maternal allergy, whilst the safety of isosulfan blue in pregnant patients remains inadequately proven [37].

The fetal hazards linked to breast surgery during pregnancy are typically minimal, but may encompass: miscarriage (especially in the first trimester); premature labor; and, in rare instances, fetal development limitation.

Research assessing pregnancy outcomes in women following cancer surgery indicates that the procedure itself infrequently inflicts direct injury to the fetus, while difficulties may emerge from the severity of maternal disease or subsequent systemic treatment.

A comprehensive population-based study encompassing over 11 million births indicated that the management of pregnancy-associated cancer necessitates coordinated obstetric monitoring, although does not inherently require the termination of pregnancy [38].

Surgery is achievable in the first trimester when urgent intervention is necessary; nevertheless, this phase is addressed with increased caution due to heightened fetal susceptibility during organogenesis and a comparably elevated chance of miscarriage. Current evaluations of breast cancer during pregnancy indicate that, when clinically permissible, therapy can be postponed until the second trimester due to reduced risks of fetal deformity and abortion; nonetheless, aggressive illness may necessitate earlier intervention [29,39].

The second trimester is typically regarded as the most advantageous period for surgery. Obstetric and perioperative literature uniformly identifies this trimester as the safest phase for non-obstetric surgery, as the risk of spontaneous miscarriage has diminished and the risk of procedure-related preterm labor is lower than in later stages of gestation. Recent evaluations on pregnant breast cancer indicate that surgery is deemed safe during all trimesters, although it is preferably conducted after 12 weeks of gestation to enhance outcomes and reduce the risk of miscarriage [40,41,42].

During the third trimester, surgery remains feasible; however, it necessitates enhanced collaboration with obstetrics due to the primary concerns regarding uterine activity, premature labor, maternal positioning, and perioperative fetal monitoring. ACOG advises perioperative surveillance for indications of preterm labor, and when the fetus is viable, monitoring of fetal heart rate and contractions should be contemplated prior to and following surgery, with intraoperative monitoring tailored to gestational age, procedure type, and local proficiency. Recent reviews on breast cancer during pregnancy similarly underscore the importance of multidisciplinary planning, optimal left lateral placement, and the coordination of surgical intervention with delivery planning as gestation nears fetal development [34,41].

Pregnancy is linked to a physiological hypercoagulable condition, marked by elevated procoagulant factors, diminished fibrinolytic activity, and venous stasis, which combined heighten the risk of venous thromboembolism (VTE). The risk of thromboembolic events during pregnancy and the postpartum period is considered to be four to five times greater than in nonpregnant women [34,43,44,45].

This risk is especially pertinent in the context of surgery, as both pregnancy and surgical procedures independently elevate thrombotic risk. Current obstetric and perioperative recommendations propose that pregnant patients having non-obstetric surgery be assessed for VTE risk and receive appropriate perioperative thromboprophylaxis when warranted [34,46,47].

Preventive measures encompass early mobilization, sufficient hydration, and tailored pharmacologic thromboprophylaxis—predominantly utilizing low-molecular-weight heparin for high-risk patients—while meticulously weighing the risk of hemorrhage. These interventions are especially crucial for patients with supplementary risk factors, including obesity, advanced maternal age, protracted immobility, or a history of thromboembolic disease [48,49,50].

3.6. Fetal Monitoring

Fetal monitoring should be contemplated during the perioperative phase whenever gestational age permits, especially after the attainment of fetal viability, to evaluate fetal well-being and enhance mother positioning, oxygenation, and hemodynamic management. The predominant guidance from ACOG indicates that for a previable fetus, it is typically adequate to record fetal heart rate via Doppler before and after surgery; conversely, for a viable fetus, concurrent electronic fetal heart rate and contraction monitoring should be conducted at least before and after the procedure. ACOG additionally states that intraoperative electronic fetal monitoring may be warranted when the fetus is viable, monitoring is technically feasible, a clinician with cesarean delivery privileges is readily available, and the planned procedure can be safely interrupted if urgent delivery is required. [34]

Intraoperative fetal monitoring should not be administered consistently in a rigorous manner; instead, it should be tailored according to gestational age, surgical complexity, anticipated maternal hemodynamic changes, available institutional resources, and the patient's preferences. Modern anesthesia reviews underscore that the choice to implement intraoperative fetal heart rate monitoring must be determined by a multidisciplinary team, as anesthetic agents may diminish baseline fetal heart rate variability, and isolated tracing alterations do not inherently signify fetal distress or necessitate delivery [51,52].

Available information indicates that intraoperative fetal monitoring is most informative when analyzed within the framework of mother physiology. A 2019 systematic study indicated that non-reassuring intraoperative fetal heart rate patterns during antepartum non-obstetric surgery were primarily attributable to maternal variables, and no intraoperative cesarean deliveries were necessitated simply due to these alterations. Nevertheless, due to a minority of patients necessitating delivery within 48 hours postoperatively, the authors determined that postoperative fetal surveillance should be contemplated, particularly in instances of expected maternal instability [53,54].

3.7. Reconstruction Considerations

Immediate breast reconstruction during pregnancy is contentious and is not usually advised for all individuals. Surgeons typically choose delayed reconstruction because to the unanticipated alterations in breast volume, ptosis, vascularity, and nipple-areolar shape associated with pregnancy, which may compromise surgical planning and aesthetic results. Moreover, prolonged reconstructive surgeries may elevate maternal anesthetic exposure and perioperative physiological strain, thereby making fetal safety a paramount concern [29,55].

Specific instances of immediate repair, especially with a tissue expander, have been documented to yield satisfactory mother and fetal results when meticulously orchestrated by a multidisciplinary team. The most extensive published series documented 13 pregnant women who underwent rapid reconstruction following mastectomy, predominantly utilizing a two-stage expander-based technique; no significant surgical problems, spontaneous miscarriages, or major congenital anomalies were recorded.[56] A distinct case series and case-based study similarly determined that immediate reconstruction may be viable for meticulously chosen patients, however the majority of documented cases employed tissue expanders instead of definitive reconstruction [55,57].

Consequently, the most judicious strategy is to customize reconstructive planning. Delayed reconstruction is the favored approach in numerous centers, whereas immediate expander-based reconstruction may be contemplated for carefully selected patients following comprehensive counseling about operative duration, cosmetic unpredictability during pregnancy and lactation, and the potential necessity for revision surgery post-delivery [29,55,56].

3.8. Oncological Treatment

Management of PABC must include gestational age, as fetal susceptibility to oncologic therapies varies considerably across the trimesters. Therapeutic planning necessitates the equilibrium of effective maternal cancer treatment while reducing fetus harm. Current international guidelines underscore that treatment should adhere to standard oncologic principles whenever feasible, while tailoring medication to the stage of pregnancy [10].

3.8.1. First Trimester limitations

The first trimester (up to 12–14 weeks) encompasses the period of fetal organogenesis and signifies the phase of greatest vulnerability to teratogenic effects. Exposure to cytotoxic chemicals during this period has been linked to a heightened risk of significant congenital abnormalities and pregnancy loss. Therefore, chemotherapy is typically contraindicated in the first trimester [10,29].

Radiotherapy is prohibited during pregnancy, especially in early gestation, due to the potential for fetal radiation exposure to produce teratogenic effects, growth restriction, or neurological damage [58,59].

3.8.2. Second trimester limitations

The second trimester is typically regarded as the safest phase for systemic oncologic therapy during pregnancy. At this period, embryonic organogenesis is mostly complete, diminishing the likelihood of significant congenital abnormalities linked to chemotherapy exposure. Numerous research and worldwide consensus declarations indicate that anthracycline-based chemotherapy regimens can be provided with considerable safety during the second and third trimesters [60,61].

3.8.3. Third Trimester

In the third trimester, systemic therapy may proceed with vigilant monitoring of both maternal and fetal conditions. Chemotherapy should often be halted around three weeks prior to the anticipated delivery to decrease the risk of maternal myelosuppression, newborn cytopenia, and infectious problems at birth [10,62].

3.8.4. Chemotherapy

The safety of chemotherapy during pregnancy is contingent upon various interrelated aspects, including placental drug transfer, maternal-fetal pharmacokinetics, and the timing of exposure in relation to fetal development. Historically avoided, recent clinical evidence indicates that specific chemotherapeutic agents can be administered with relative safety during the second and third trimesters, contingent upon individualized treatment decisions made by a multidisciplinary team comprising oncologists, obstetricians, and neonatologists [63].

Fetal exposure to anticancer drugs generally occurs via transplacental diffusion from the maternal bloodstream. The degree of prenatal exposure is determined by many pharmacologic properties of the drug, such as molecular weight, lipid solubility, protein binding, and ionization state. Furthermore, the placenta serves as a dynamic metabolic and transport barrier, exhibiting many efflux transporters, including P-glycoprotein and breast cancer resistance protein (BCRP), which can actively diminish fetal drug accumulation [64].

Maternal physiological alterations during pregnancy—such as elevated plasma volume, modified hepatic metabolism, and improved renal clearance—can further influence the pharmacokinetics of chemotherapeutic drugs. These alterations may impact drug distribution and elimination, potentially affecting both maternal treatment effectiveness and fetal exposure [65,66].

The extent of placental translocation significantly differs among chemotherapeutic drugs. Anthracyclines, including doxorubicin and epirubicin, are the cornerstone of systemic therapy for breast cancer in pregnancy and are often linked to minimal fetal exposure owing to their considerable molecular weight and active placental efflux mechanisms [67].

Recent evidence indicates that specific taxanes, such as paclitaxel and docetaxel, have limited placental transfer, potentially enhancing their safety profile when administered post-first trimester. In clinical studies and comprehensive reviews, the administration of taxanes throughout the second and third trimesters has not been linked to a heightened incidence of significant congenital abnormalities, while long-term developmental data are still scarce [64,68].

The timing of chemotherapy in relation to gestational age is the most significant factor influencing fetal risk. The initial trimester, specifically weeks 2 to 12 of gestation, exhibits the greatest vulnerability to teratogenic damage. Exposure to cytotoxic drugs during this phase has been linked to elevated rates of miscarriage, fetal demise, and significant congenital anomalies [67].

Upon the conclusion of organogenesis, the teratogenic risk associated with chemotherapy diminishes significantly. Observational studies and clinical registries suggest that chemotherapy given during the second and third trimesters correlates with rates of congenital malformations similar to those in the general population, although complications such as prematurity or low birth weight may arise [69,70,71].

Systemic therapy during pregnancy is often commenced during 12–14 weeks of gestation, following the completion of organogenesis. Chemotherapy is often halted around three weeks before to the expected delivery to facilitate maternal bone marrow recovery and mitigate the risk of neonatal cytopenias or infection problems [72,73,74].

3.8.5. Recommended Chemotherapy Regimens

Among the systemic pharmaceuticals for PABC, anthracycline-based regimens are the most established and commonly endorsed chemotherapy methods. These regimens often integrate an anthracycline—predominantly doxorubicin or epirubicin—with cyclophosphamide, and have been widely employed in both adjuvant and neoadjuvant contexts for pregnant patients diagnosed in the second and third trimesters [63,75].

The predominant chemotherapy regimens for gestational breast cancer consist of doxorubicin combined with cyclophosphamide (AC) and epirubicin paired with cyclophosphamide (EC), which constitute the foundation of traditional breast cancer treatment protocols [75]. These regimens are typically favored due to the low placental transfer and good fetal safety profile of anthracyclines like doxorubicin and epirubicin when given during the second or third trimester, while preserving effective anticancer activity [75,76,77].

Consequently, prominent oncology consensus statements and multidisciplinary guidelines uniformly advocate for anthracycline-based chemotherapy as the primary systemic treatment for breast cancer identified during pregnancy, with therapy generally commencing post-organogenesis [63].

Taxanes, such as paclitaxel and docetaxel, are extensively utilized in contemporary breast cancer chemotherapy regimens and have progressively been integrated into treatment protocols for pregnancy-associated breast cancer. Despite initial concerns about fetal safety due to limited early experience with these agents in pregnancy, recent clinical evidence over the past decade indicates that taxane administration during the second and third trimesters is feasible and relatively safe when appropriately selected and monitored [63,64].

The pharmacological characteristics of taxanes may partially elucidate their satisfactory safety profile during gestation. Experimental and clinical investigations demonstrate that placental efflux transporters, including P-glycoprotein, restrict the transplacental transfer of paclitaxel and docetaxel, therefore diminishing fetal exposure [64,78]. In clinical series and registry analyses, the administration of taxanes after the first trimester has not been linked to a heightened incidence of significant congenital malformations; nonetheless, issues attributable to prematurity or treatment-associated maternal toxicity may still arise [63].

Recent observational studies and worldwide cohort analyses have further corroborated the safety of taxanes during pregnancy. Retrospective investigations of pregnant patients administered paclitaxel or docetaxel during the second or third trimester revealed maternal toxicity profiles akin to those in non-pregnant individuals, with no increase in short-term maternal-fetal problems [79].