Phyllodes tumors of the breast are uncommon fibroepithelial neoplasms that account for roughly 0.3 to 0.5 percent of all primary female breast tumors, with an estimated incidence of 2.1 per million women in the United States, or about 500 cases per year. They typically arise in women between 35 and 55 years of age, which makes their appearance in a 23-year-old particularly noteworthy. The World Health Organization classifies these tumors into benign, borderline, and malignant variants, a distinction based on cellular atypia, the infiltrative character of tumor margins, and mitotic frequency. The malignant form, which constitutes between 6.5 and 27 percent of all phyllodes tumors, carries a higher propensity for local recurrence and for distant metastasis, most often to the lungs. Local recurrence is associated with an increased risk of death, while metastatic disease carries a dismal prognosis.

The patient in this report first noticed an abnormality in her right lateral breast by self-palpation. When the mass began to enlarge and became painful in the fall of 2023, she sought medical attention. On physical examination, her breasts were mildly asymmetric with grade A ptosis, and a large mass occupied the entire upper outer quadrant of the right breast, without skin changes, nipple discharge, or nipple inversion. She was premenopausal, had never been pregnant, and had no history of breast surgery, biopsy, or radiation. Interestingly, pain at the tumor site is atypical for phyllodes tumors, as most patients report an enlarging but painless mass, making her presentation somewhat unusual.

Diagnostic ultrasound of the right breast confirmed a suspicious finding: a large heterogeneous, predominantly hypoechoic mass, or possibly a conglomerate of masses. Ultrasound-guided biopsy identified a fibroepithelial neoplasm measuring 6.8 by 2.9 by 6.4 centimeters, located at the 9 to 10 o’clock position, 3 centimeters from the nipple. No suspicious abnormality was found in the right axilla. A surgeon performed a right breast lumpectomy with minimal external incisions, since the patient formed keloids readily. Pathology of the excised tissue, which measured 10.0 by 5.8 by 5.2 centimeters, was most consistent with a primary malignant phyllodes tumor, showing atypical spindle cell proliferation extending to both the inferior and medial margins. Mitotic activity reached 28 mitoses per 10 high-power fields, and the tumor displayed stromal expansion with increased stromal cellularity and mild to moderate atypia, though without definitive stromal overgrowth. A contrast-enhanced chest CT showed no metastatic disease.

Because residual tumor remained in the region of the prior lumpectomy, spanning 7.0 centimeters with a posterior margin of only 0.25 millimeters, the patient underwent a skin- and nipple-sparing simple mastectomy with immediate placement of a prepectoral tissue expander. Medical oncology did not recommend adjuvant chemotherapy, reflecting the limited evidence supporting systemic therapy in this disease. Instead, after a detailed discussion of risks and benefits, she consented to adjuvant radiotherapy to the right chest wall to reduce the risk of local recurrence. Genetic testing revealed variants of uncertain significance in four genes: PMS2, POLE, SDHA, and SMARCA4. Because these were classified as variants of uncertain significance, they could not inform clinical decision-making, although the authors note that loss of SDHA function has been observed in renal cell carcinoma, the same cancer her maternal grandfather had.

The radiotherapy regimen was technically sophisticated. Using volumetric modulated arc therapy with 6-megavolt photons, the patient received 5,000 cGy in 25 fractions to the right chest wall, followed by a 1,000 cGy boost in 5 fractions targeting the right central and upper medial quadrants and the mastectomy scar line, for a plan sum of 6,000 cGy. Nineteen of the initial fractions were delivered without a bolus, while 6 fractions incorporated a 0.5-centimeter bolus with a specific gravity of 1.02. The bolus is a tissue-equivalent material placed on the skin surface to counteract the skin-sparing effect of high-energy beams, increasing the superficial dose where tumors or close margins lie near the skin. Dosimetric analysis showed excellent protection of organs at risk: the right lung V20 was 16.5 percent across the plan sum, the mean heart dose was only 206.6 cGy, and the D95 percent dose to the chest wall skin reached 3,748.5 cGy. All plans were created by a certified medical dosimetrist and reviewed by the radiation oncologist and a qualified medical physicist, with all constraints met.

The decision to use a bolus rested on a specific geometric problem. The close posterior margin lay in the upper medial portion of the right chest wall, where little distance separated the skin from the chest wall and pectoralis muscle. The tissue expander covered part of the region, but a portion of the concerning area sat flat against the chest wall, and without a bolus, full dose could not be delivered there. A systematic review by Dahn and colleagues found that although high-quality literature on post-mastectomy radiotherapy with a bolus is lacking, a bolus may be recommended for tumors with high-risk features such as skin involvement or positive margins to achieve adequate superficial dose and reduce local recurrence. While this patient had neither skin involvement nor a positive margin, the combination of a very close margin, stromal atypia, high mitotic activity, and a body habitus and expander position that prevented full-dose coverage justified the technique.

The fractionation strategy also reflected a deliberate toxicity trade-off. Daily use of a 0.5-centimeter bolus is significantly associated with grade 3 radiation dermatitis, so limiting the bolus to 6 of 30 fractions reduced that risk. The authors note that thicker 1.0-centimeter boluses tend to increase toxicity when used daily, and that in patients with tissue expanders there is no significant difference in wet desquamation or grade 3 dermatitis between bolus and no-bolus approaches. The patient tolerated treatment well, experiencing soreness, itchiness, grade 2 radiation dermatitis, skin hyperpigmentation without wet desquamation, and fatigue. Trental and vitamin E were prescribed to prevent radiation fibrosis, though Trental was discontinued early due to nausea.

At twelve months after the initial abnormality was discovered, the patient had healed well, undergone implant exchange with placement of a smaller contralateral implant for symmetry, and remained active and working with good range of motion. She continues physical therapy to break up scar tissue and reduce lymphedema risk, and her circulating tumor DNA assay, Signatera, was negative with no evidence of disease. The case adds to the scarce literature on young adults with malignant phyllodes tumors and illustrates a practical use case for bolus-enhanced adjuvant radiotherapy. Because malignant phyllodes tumors are more aggressive and recur locally more often than other phyllodes variants, the authors argue that bolus-assisted post-mastectomy radiotherapy deserves consideration in patients with high-risk features, particularly when tissue expander position or body habitus makes full-dose coverage of close margins difficult to achieve otherwise.

Subject of Research: Adjuvant radiotherapy with a bolus for malignant phyllodes tumor of the breast in a young adult

Article Title: Young Adult With Malignant Phyllodes Undergoing Adjuvant Radiotherapy With Bolus

Article References: Young Adult With Malignant Phyllodes Undergoing Adjuvant Radiotherapy With Bolus. (n.d.). https://doi.org/10.1002/ccr3.73471

Image Credits: AI Generated

DOI: 10.1002/ccr3.73471

Keywords: phyllodes tumor, breast cancer, adjuvant radiotherapy, bolus, mastectomy, VMAT, young adults, local recurrence, radiation dermatitis, tissue expander, fibroepithelial neoplasm, case report