Phyllodes tumors of the breast: a comprehensive review

Abstract

Phyllodes tumors are rare biphasic fibroepithelial breast neoplasms classified as benign, borderline, or malignant. Despite their rarity, malignant variants carry higher risks of recurrence and metastasis. This review synthesizes current evidence on their clinical, histopathological, and molecular characteristics, including treatment strategies and prognostic factors, emphasizing tailored management. We performed a comprehensive literature review to summarize knowledge on clinical presentation, imaging, histopathological features, surgical treatment, adjuvant therapy, and outcomes. Recent genomic and molecular research was also evaluated to identify future directions. Persistent challenges include a lack of consensus on optimal surgical margins, adjuvant radiotherapy, and follow-up protocols, highlighting the need for larger, high-quality studies. Advances in molecular profiling suggest potential for targeted therapies, especially in aggressive or metastatic cases. Due to clinical heterogeneity and the limited accuracy of core biopsies, definitive grading based on surgical histopathology remains essential for treatment planning. This review offers an updated perspective on phyllodes tumor management, identifies critical gaps, and suggests priorities for future research.

INTRODUCTION

Phyllodes tumors (PTs) are biphasic fibroepithelial neoplasms of the breast, characterized by a distinctive leaf-like (phylloidal) epithelial pattern and prominent stromal proliferation. First described by Johannes Müller in 1838 as “cystosarcoma phyllodes,” they were initially misclassified as benign fibroadenomas [1]. By the mid-20th century, histopathological criteria allowed for clearer differentiation based on stromal features such as cellular atypia, mitotic activity, and overgrowth [2].

In 1981, the World Health Organization (WHO) established a classification system for PTs—benign, borderline, and malignant—based on mitotic rate, stromal cellularity, and tumor border. This framework remains the cornerstone for diagnostic and therapeutic decision-making, although refined over time (Table 1).

Table 1. Summary of the changes in the World Health Organization (WHO) classification of phyllodes tumors.

Epidemiologically, PTs are rare, with an incidence rate of 2.1 per million women, the peak age of 45 to 49 years [2,3]. They constitute approximately 1% of all breast tumors, with the majority being benign (60%–75%), followed by borderline (15%–26%) and malignant (8%–20%) subtypes [2]. These tumors typically present in women aged 40–50 years (range, 13–103 years), though benign PTs are more likely to occur at a younger age compared to their borderline and malignant counterparts. The etiology of PTs remains unclear, but an increased incidence has been reported in patients with Li-Fraumeni syndrome, suggesting a potential genetic link [4].

Given their rarity and diverse clinical behavior, PTs pose ongoing challenges in diagnosis and management. Key controversies include the optimal width of surgical margins—particularly in borderline and malignant cases—the role of adjuvant radiotherapy (RT), and the absence of standardized surveillance protocols. Moreover, while most patients present with localized disease, a subset of aggressive tumors exhibits high metastatic potential and lacks established systemic treatment strategies. Recent molecular studies have identified recurrent genetic alterations, including TP53, EGFR, and TERT promoter mutations, predominantly in malignant subtypes [5]. These findings have spurred efforts to develop risk stratification models and targeted therapies based on molecular profiling. However, their clinical application remains investigational, and further prospective studies are needed to establish their utility in guiding personalized treatment.

This review provides an updated synthesis of clinical, histopathological, and molecular aspects of PTs, with a focus on current management controversies and future directions.

METHODS

We conducted an extensive review of the literature to summarize key aspects of PTs, including clinical presentation, radiologic findings, histopathological features, surgical management, adjuvant therapy, postoperative outcomes, and surveillance strategies. In addition, recent genomic and molecular studies were examined to highlight emerging insights and future directions in diagnosis and treatment.

RESULTS

Clinical presentation

PTs typically present as rapidly growing, palpable, painless, and well-defined breast masses, most commonly in middle-aged women, with an average tumor size of approximately 6 cm [2,3]. While some patients remain asymptomatic, others may experience symptoms such as breast pain or discomfort, particularly as the tumor enlarges or affects adjacent tissues. Although the clinical presentation of PTs does not strongly correlate with histological grade, factors such as rapid growth, larger tumor size, and a history of prior fibroadenoma or benign PT surgery may increase the likelihood of borderline or malignant pathology [6]. However, this correlation is not consistently observed in all cases.

In imaging studies, PTs often resemble fibroadenomas, particularly on ultrasound or mammography, where they typically appear as hypoechoic, oval masses. However, certain distinguishing features—such as lobulations, heterogeneous internal texture, cystic components, and hyperechoic septae—may aid in differentiation. On mammography, PTs usually appear as well-defined, high-density masses that can sometimes mimic cysts, fibroadenomas, or well-circumscribed carcinomas. Despite these characteristics, mammography has limited sensitivity (31%–70%) in distinguishing PTs from fibroadenomas, especially in benign cases [3]. MRI may offer additional information to differentiate between fibroadenomas and PTs and provide insights into tumor size and local extent, but radiologic findings alone generally cannot reliably distinguish benign from malignant PTs [3]. Although features such as a tumor size greater than 10 cm and increased vascularity on Doppler ultrasound may suggest malignancy, imaging modalities alone cannot reliably predict the malignant potential of PTs [3]. Thus, histopathological confirmation remains essential.

Core needle biopsy (CNB) is frequently used to help distinguish fibroadenomas from PTs, though its diagnostic accuracy varies widely, ranging from 13% to 84% [7]. Due to overlapping histological features and tumor heterogeneity, CNB may occasionally yield inconclusive results, leading to a classification of the lesion as a fibroepithelial tumor with a recommendation for complete surgical excision to achieve a definitive diagnosis. Excisional biopsy provides a more extensive tissue sample, allowing for thorough histopathological evaluation and reducing the risk of misdiagnosis. Ultimately, histopathological assessment is essential to accurately differentiate benign, borderline, and malignant PTs and ensure appropriate treatment. Although imaging techniques are useful for initial evaluation, they remain limited in distinguishing PT subtypes. Consequently, when CNB results are inconclusive or insufficient, surgical excision is often required to provide a more conclusive assessment.

Epithelial and stromal interactions and progression to malignant forms

Epithelial and stromal interactions in PTs play a critical role in tumor progression, particularly in the transition from benign to malignant forms. PTs are distinctive fibroepithelial neoplasms where the interplay between stromal and epithelial components shapes growth patterns. Sawhney et al. [8] proposed that stromal growth in PTs may initially depend on the epithelial component, with malignancy developing as the stromal component gains independence. Further study [9] has shown allelic imbalances in both compartments, linking benign proliferation with the Wnt signaling pathway. As tumors progress to malignancy, stromal proliferation appears to become uncontrolled, likely due to the loss of Wnt5a signaling and increased growth factor receptor activity.

Growth factor signaling between epithelial and stromal components has also been shown to contribute to tumor aggressiveness and prognosis. Feakins et al. [10] identified coexpression of platelet-derived growth factor (PDGF) in the epithelial component and PDGF receptor-β in the stromal component, correlating with poorer outcomes, including disease-related death in certain PT cases. Additionally, elevated levels of CXCR4, a molecule associated with epithelial-stromal interactions, have been observed in the stromal component of high-grade PTs, suggesting its potential as a biomarker for aggressiveness [8,9].

Histopathological features and differential diagnosis between phyllodes tumor subtypes

PTs are histologically characterized by biphasic architecture, with epithelial and stromal components. Diagnostic criteria include stromal overgrowth, stromal cellularity, nuclear atypia, mitotic activity, and tumor borders. Malignant variants display increased mitotic activity, pronounced stromal overgrowth, and may include heterologous elements such as sarcomatous differentiation [2]. Based on these histologic features, PTs are classified into benign, borderline, and malignant categories. Notably, histologic grade does not always align with clinical behavior, as benign tumors may recur with features of higher grade. Figs. 1, 2, 3, 4 present cases with overlapping clinical and imaging features, including rapidly growing palpable masses and well-circumscribed, oval lesions. These similarities highlight that clinical and radiologic findings alone are insufficient to distinguish benign, borderline, and malignant PTs, underscoring the importance of histopathological assessment.

Fig. 1. Imaging and pathological findings of a 59-year-old woman with a benign phyllodes tumor. (A) A round, partially indistinct, circumscribed hyperdense mass (mammography). (B, C) Pathological features displaying a leaf-like architecture with low stromal cellularity (B; H&E stain, ×40; scale bar, 500 µm) and subepithelial stromal condensation with increased stromal cellularity adjacent to the epithelium and low mitotic activity (C; H&E stain, ×200; scale bar, 100 µm; red circle, mitotic figure). The slides were scanned using a Leica GT 450 scanner (Leica) and images were captured using Sectra IDS7 (Sectra).

Fig. 2. Imaging and pathological findings of a 51-year-old woman with a borderline phyllodes tumor. (A, B) An oval-shaped, circumscribed hyperdense mass (A, mammography) and a heterogeneously enhancing mass involving the entire right breast (B, MRI). (C, D) Pathological features showing moderate stromal cellularity (C; H&E stain, ×40; scale bar, 500 µm) and moderate stromal atypia with mitotic figures (D; H&E stain, ×400; scale bar, 50 µm; red circles, mitotic figures). The slides were scanned using a Leica GT 450 scanner (Leica) and images were captured using Sectra IDS7 (Sectra).

Fig. 3. Imaging and pathological findings of a 47-year-old woman with a malignant phyllodes tumor harboring PTEN (Y68C) and TP53 (C229fs) mutations. (A, B) A round-shaped hyperdense mass (A, mammography) and a rimenhancing mass with multifocal enhancing nodules (B, MRI). (C, D) Pathological features displaying infiltrative tumor borders (C; H&E stain, ×40; scale bar, 500 µm) and multinucleated giant cells, nuclear atypia, and increased mitotic activity (D; H&E stain, ×400; scale bar, 50 µm; red circles, mitotic figures). The slides were scanned using a Leica GT 450 scanner (Leica) and images were captured using Sectra IDS7 (Sectra).

Fig. 4. Imaging and pathological findings of a 45-year-old woman with a malignant phyllodes tumor harboring a TP53 mutation (H214R). (A, B) An oval, relatively circumscribed, heterogeneous hypoechoic mass with posterior acoustic enhancement (A, ultrasound) and a rim-enhancing mass (B, MRI). (C, D) Pathological features showing marked stromal overgrowth with no epithelial component visible (C; H&E stain, ×400; scale bar, 500 µm) and high stromal cellularity with brisk mitotic activity (D; H&E stain, ×400; scale bar, 50 µm; red circles, mitotic figures). The slides were scanned using a Leica GT 450 scanner (Leica) and images were captured using Sectra IDS7 (Sectra).

Benign phyllodes tumors

Benign PTs exhibit mild stromal cellularity, minimal nuclear atypia, and a mitotic rate of fewer than 5 mitoses per 10 high-power fields (HPF) (Fig. 1). Stromal overgrowth is typically absent, and epithelial elements are preserved. Tumor margins are generally well-circumscribed and noninvasive. Differentiation from cellular fibroadenomas can be challenging, as both may show increased stromal cellularity. However, benign PTs typically display more uniformly cellular stroma with monomorphic spindle-cell nuclei and a low mitotic index. Stromal cellularity is often accentuated around the epithelial components, and features such as stromal hyalinization or myxoid change may aid in distinction (Table 2).

Table 2. Histopathological differentiation and diagnostic parameters of fibroepithelial tumors of the breast.

NA, not applicable; HPF, high-power field.

Borderline phyllodes tumors

Borderline PTs represent an intermediate histologic category. They display moderate stromal cellularity, mild to moderate atypia, and a mitotic count of 5–9 mitoses per 10 HPF (Fig. 2). Focal stromal overgrowth may be seen, and tumor borders are often pushing or partially infiltrative.

Malignant phyllodes tumors

Malignant PTs show marked stromal cellularity, pronounced nuclear atypia, and frequent mitoses—typically more than 10 per 10 HPF (Figs. 3, 4). Stromal overgrowth is often extensive, with complete loss of epithelial structures in certain regions. Tumor borders are usually infiltrative, and heterologous elements such as liposarcomatous or osteosarcomatous differentiation may be present in some cases (Table 2).

Surgical management and resection margins

Surgical excision is the primary treatment for PTs, yet the optimal extent of resection and width of surgical margin remains debated, particularly regarding their impact on local recurrence (LR) and overall outcome. While benign PTs can often be managed with margin-negative resections, borderline and malignant PTs typically require more aggressive approaches, such as wide local excision or mastectomy. While achieving clear surgical margins is essential to reduce recurrence rates, the necessity of wide margins remains a subject of debate.

According to the National Comprehensive Cancer Network (NCCN) guidelines, a surgical margin of ≥1 cm is recommended regardless of PT type or size [11]. Recent studies, however, show varied recurrence rates with different margin widths. Some studies suggest that larger margins (>1 cm) may further reduce recurrence in borderline and malignant PTs, whereas others indicate that smaller but clear margins may suffice [12,13,14]. The optimal margin threshold is still under exploration due to variability in PT behavior.

Surgical considerations in benign and borderline phyllodes tumors

Lu et al. [15] found that LR rates were similar between ultrasound-guided vacuum-assisted biopsy and surgical excision for benign PTs. Their meta-analysis also indicated a strong association between positive margins and higher recurrence in malignant PTs, with only a weak trend observed in benign and borderline PTs. Balogun et al. [16] reported no significant difference in recurrence rates between positive and negative margins for benign and borderline PTs. A recent multi-institutional study showed that, in cases with PTs and positive margins where re-excision was not performed, only a small fraction (2.7%) experienced LR [17].

However, high-risk factors such as larger tumor size (>4 cm) or stromal overgrowth make achieving negative surgical margins more critical for reducing recurrence [15,17,18]. This suggests that while surgical margins alone may not be decisive for all benign and borderline PTs, they become more important with additional risk factors based on tumor characteristics. Reflecting these findings, the NCCN guidelines recently advised that routine re-excision may not be necessary for benign PTs with positive margins. Still, re-excision is considered beneficial in recurrent cases to prevent progression to more aggressive forms [11].

For borderline PTs, a meta-analysis by Toussaint et al. [18] found that LR risk was higher with resection margins less than 10 mm. The study reported a 5-year LR rate of 9.6% for margins <10 mm, compared to 7.33% for margins ≥10 mm. Tumor size is also a significant factor, with larger tumors (>5 cm) having higher recurrence rates, warranting wider margins (>1 cm) in these cases.

Surgical approach in malignant phyllodes tumors

There are no randomized trials specific to PTs, but studies show that malignant PTs carry a significantly higher risk of recurrence. LR rates for malignant PTs range from 15% to 40%, with 9% to 27% of malignant PTs metastasizing even after margin-negative resections [15]. Most evidence suggests that surgical factors, such as the type of operation and surgical margin status, are primarily associated with local control rather than distant recurrence or overall survival (OS). Wide local excision or mastectomy is typically performed, with margin-negative resections being critical to reduce LR. A meta-analysis [15] demonstrated that malignant PTs with margins <10 mm had a 5-year recurrence rate of 28.6%, compared to 21.8% for those with ≥10 mm margins. The NCCN recommends a target margin of 1 cm for malignant PTs, though mastectomy is not always required if partial mastectomy fails to reach 1 cm margins [11].

In cases of recurrent PTs, repeat wide excision or breast conservation may be effective, although 30% of patients experience re-recurrence [19]. Belkacémi et al. [19] observed that of 76 patients with recurrence, 70 (92.1%) required salvage mastectomy after re-recurrence, highlighting that while breast conservation can be effective, mastectomy may be necessary in cases of re-recurrence. Currently, there is no strong evidence supporting the specific indication of adjuvant therapies for recurrent PTs.

Axillary surgery

Regional lymph node enlargement is relatively common in PTs, but lymph node metastasis remains extremely rare. Norris and Taylor [20] reported axillary lymph node metastasis in only 1% of all PT cases, although lymphadenopathy was observed in 17% of cases, likely due to reactive hyperplasia rather than true metastasis. A SEER data analysis from 2000 to 2020 by Yang et al. [21] on 2,261 patients with malignant PTs further corroborated this, showing lymph node involvement in only 2.1% of cases. Given these findings, routine axillary surgery is generally not recommended. Additionally, sentinel lymph node biopsy has not demonstrated clinical significance for PTs, and its routine use is not advised. Selective lymph node removal or excisional biopsy is reserved for cases with suspicious or palpable nodes.

Recurrence and prognostic factor

PTs of the breast exhibit variable recurrence risks depending on histologic grade, with LR rates and survival outcomes differing significantly among benign, borderline, and malignant forms. The WHO reports an overall LR rate of approximately 21%, with recurrence rates around 10%–17% for benign, 14%–25% for borderline, and 23%–30% for malignant PTs [2,12]. A recent meta-analysis by Lu et al. [15] supports these findings, reporting pooled LR rates of 8% for benign, 13% for borderline, and 18% for malignant PTs. Table 3 consolidates key studies, providing essential data on recurrence and progression risks to guide individualized patient management [6,12,13,17,22].

Table 3. Outcomes and prognostic indicators in PTs: data from retrospective studies.

PT, phyllodes tumor; NA, not applicable; LR, local recurrence; DM, distant metastasis; CSS, cause-specific survival; HPF, high-power field.

LR rates in PTs have been associated with various factors across studies, including tumor grade, surgical margin status, type of surgery, and pathologic features such as mitotic rate, tumor border characteristics, stromal cellularity, stromal atypia, stromal overgrowth, and tumor necrosis. However, the specific parameters and outcomes for each factor vary between studies, leading to inconsistent findings. Some studies emphasize surgical margin status and treatment modalities [6,13], while others emphasize histologic parameters such as mitotic index or cellular atypia [12,17]. Additionally, several studies classify risk based on patient factors like age or tumor size [6,22], further contributing to variability in reported outcomes.

Distant metastasis is a significant concern primarily for malignant PTs, with reported rates varying widely, ranging from approximately 3% to 60% [17,18]. The most common metastatic sites include the lungs (66%), bones (28%), and brain (9%), with less frequent involvement of the liver and heart [23]. These metastases typically occur via hematogenous spread and often develop without preceding LR. Adverse histopathologic features, such as stromal overgrowth, high mitotic rates, and infiltrative tumor borders, correlate with an increased risk of metastasis and poorer prognosis [6,20]. Patients with metastatic malignant PTs generally have poor outcomes due to the limited responsiveness of these tumors to conventional chemotherapy, contributing to higher mortality rates in this subgroup.

Survival outcomes for PTs vary substantially by grade. Benign and borderline PTs exhibit excellent disease-specific survival, with 5-year survival rates of 96%–100% and 91%–95%, respectively. In contrast, malignant PTs show a broader range of prognosis, with 5-year OS rates reported between 5%–60% and 97%, reflecting the variability in distant recurrence risk [15,23]. This variability in recurrence, metastasis, and survival outcomes points to the need for a tailored approach that incorporates histologic grade and patient-specific factors, along with the development of unified clinical guidelines to manage diverse risk profiles and guide optimal treatment and follow-up.

Histologic upgrade or grade progression of recurrent phyllodes tumors

Histologic upgrade or grade progression in PTs is a notable phenomenon, with multiple studies documenting increased histologic severity in recurrent cases. Grade progression has been reported in 16%–31.5% of recurrent PTs, with cases advancing from benign to borderline or malignant forms [2,15,17]. Rosenberger et al. [17] observed that 20% of locally recurrent PTs underwent histologic upgrades, with benign tumors progressing to borderline grades and borderline to malignant. Additionally, Choi et al. [24] found that 26% of borderline PTs recurred as malignant, while 70% of initially malignant PTs recurred at the same grade. Barrio et al. [25] reported that 6 of 23 locally recurrent benign PTs underwent malignant transformation, with high stromal cellularity and mitotic rates correlating with an increased risk of upgrade.

These findings suggest that histologic progression may be influenced by factors such as insufficient initial tumor sampling, dedifferentiation, and complex epithelial-stromal interactions. While most patients with benign or borderline PTs have an excellent prognosis after surgical resection, those with uniformly poor features require more careful follow-up, and novel treatment strategies may be necessary to improve outcomes in these higher-risk cases.

Surveillance

Surveillance strategies for PTs remain heterogeneous due to the absence of standardized guidelines. In clinical practice, follow-up protocols are often adapted from those used for breast adenocarcinoma or soft tissue sarcoma, leading to variability in both duration and modality. While the NCCN guidelines recommend clinical follow-up for 3 years without specifying imaging modalities [11], other sources report more intensive surveillance, often extending to 5 years and incorporating imaging such as mammography or ultrasound [26].

Surveillance intensity is generally stratified by tumor grade. Benign PTs have relatively low recurrence rates, with most recurrences occurring within 3 to 5 years postoperatively. Accordingly, a recent study by Diego et al. [26] found that approximately 48.1% of surgeons recommended follow-up for 2 years, while most others extended it to 3–5 years. In contrast, malignant and borderline PTs exhibit higher recurrence risks, particularly within the first 2 to 3 years after treatment. For these subtypes, 66% of surgeons recommend at least 5 years of surveillance, with closer monitoring during the early postoperative years.

Follow-up schedules also differ across studies, ranging from annual clinical exams and imaging to biannual evaluations during the first 2 years, followed by annual assessments thereafter (Table 4) [3,11,27,28].

Table 4. Follow-up protocols for phyllodes tumor (PT).

NCCN, National Comprehensive Cancer Network; NA, not applicable.

Adjuvant therapy

Radiotherapy

Adjuvant RT for PTs is supported by limited robust evidence, with studies primarily indicating that RT helps reduce LR rather than significantly impacting distant metastasis-free survival or OS [15,21]. A meta-analysis indicated that RT significantly reduced LR in malignant PTs, though these results have been questioned due to inconsistencies, such as conflating distant metastasis-free survival and LR events [15]. Chao et al. [29] found an 8% recurrence rate in RT-treated PTs compared to 12% in those treated with surgery alone, suggesting a modest benefit for local control. However, a recent SEER-based study of 2,261 malignant PT cases (with 455 receiving RT) found no survival advantage for RT across age groups after propensity score matching, indicating limited survival benefits [21]. Similarly, a study of stage T3 or T4 malignant PTs reported no significant effect of RT on OS or disease-specific survival, aligning with earlier findings that RT after margin-negative resection did not improve cause-specific survival compared to surgery alone [6,14].

Overall, while RT may contribute to local control in malignant PT cases—especially those with large tumors, positive margins, or adverse histologic features—its impact on long-term survival remains inconclusive. The NCCN guidelines currently recommend RT selectively, prioritizing cases where recurrence could result in significant morbidity; however, specific indications remain inadequately defined [11]. Given the limited evidence and the rarity of PTs, multicenter prospective studies are necessary to establish definitive guidelines and build consensus on the role of RT in managing PTs.

Systemic therapy

Current evidence suggests that chemotherapy has a minimal role in PT management due to its limited impact on survival outcomes. The largest prospective study to date, evaluating doxorubicin and dacarbazine in 28 patients, showed no significant improvement in recurrence-free survival compared to observation alone, suggesting that chemotherapy generally has minimal effect on PT survival outcomes [30]. Retrospective analysis supports this finding, indicating that chemotherapy is typically reserved for metastatic or treatment-refractory cases. Partial responses have been observed with regimens like MAID (mesna, doxorubicin, ifosfamide, and dacarbazine), though these responses are often accompanied by significant toxicity [31].

Endocrine therapy is also not routinely recommended due to low hormone receptor expression in the PTs’ stromal component. Immunohistochemical studies have shown estrogen receptor or progesterone receptor positivity mainly in the epithelial component (43%–84%), while stromal receptor expression is rare and inversely correlated with malignancy [32]. Since PTs are predominantly driven by the stromal component, hormonal therapy is generally ineffective, targeting cells with minimal receptor positivity. The NCCN guidelines similarly advise against routine endocrine therapy, noting limited benefits from adjuvant chemotherapy and recommending that systemic recurrences, primarily pulmonary metastases, be managed according to soft tissue sarcoma protocols [11]. Consequently, systemic treatments remain secondary to surgical resection and are generally reserved for metastatic or recurrent cases unresponsive to other treatment modalities.

Genomic insights and targetable pathways in malignant phyllodes tumors

Conventional systemic therapies have shown limited efficacy for malignant PTs, especially in metastatic cases where prognosis remains poor. Recent genomic analyses have identified actionable mutations, suggesting new avenues for targeted therapy. Kim et al. [5] identified mutations in EGFR, TP53, and MED12 in malignant PTs, with additional alterations in RARA and ZNF703 associated with LR, indicating the value of genomic profiling for malignant or metastatic PTs. A large-scale study further identified frequent mutations in the TERT promoter (69.7%), CDKN2A (45.9%), TP53 (37.8%), and NF1 (35.6%), with alterations in PIK3CA and EGFR, supporting the potential to repurpose targeted therapies approved for other cancers [33]. Notably, programmed death-ligand 1 (PD-L1) expression was observed in 21.4% of malignant PT cases, and high tumor mutational burden was identified in a subset of tumors, suggesting the possibility of using immune checkpoint inhibitors like pembrolizumab and nivolumab in advanced or recurrent cases [33].

These findings suggest that the molecular complexity of malignant PTs may be addressed through personalized therapeutic approaches. Genomic profiling of malignant PTs, especially in advanced or recurrent cases, could guide tailored therapies and clinical trial opportunities, offering hope for improved outcomes in this challenging malignancy.

Germline mutation and genetic test for predisposition

PTs of the breast have been linked with germline mutations in the TP53, BRCA1, NF1, and RB1 genes [4]. Given that TP53 mutations can impact treatment choices, especially regarding radiation therapy, these findings suggest the importance of assessing family history and considering genetic counseling for PT patients, particularly those with malignant or high-risk tumors.

CONCLUSION

Despite advancements in understanding PTs, significant challenges remain due to the lack of consensus on key aspects of PT management, including optimal surgical margins, the role of adjuvant RT, and standardized follow-up protocols. The variability in clinical practices across studies demonstrates the urgent need for large, prospective studies to establish clear guidelines. This review reveals that recent studies suggest surgical margins may not be crucial for recurrence in benign PTs and that adjuvant RT may not provide a survival benefit in malignant PTs. While PTs generally exhibit excellent survival outcomes with low rates of metastasis, there remains a critical gap in evidence-based treatment options for refractory and metastatic cases. Advances in molecular and genetic analysis hold promise for developing targeted therapies, potentially paving the way for improved outcomes in aggressive or treatment-resistant PTs.