Radiation Oncology/Breast/Phyllodes

Overview
The term phyllodes tumor, which was previously known as cystosarcoma phyllodes, refers to a group of lesions with varying metastatic potential. These tumors are quite rare. The word "phyllodes" derives from the Greek word for "leaf" and is used because the tumor has a leaf-like, lobulated appearance when sectioned.

These tumors are often very large and grow rapidly. Median age of presentation is 45 yrs, which is 20 yrs later than fibroadenomas.

Pathologically, has both epithelial and stromal components. Both must be present. It's the stromal component that has the metastatic potential.

Can be classified as benign, borderline, or malignant. This classification is based on the tumor margins (pushing=benign, infiltrative=malignant), mitotic activity, and overgrowth of stroma (which is probably the most important feature).

Lymph node metastases are rare.

Distant metastases are usually to the lung, as is the pattern seen in sarcomas.

Prognostic factors:
 * local recurrence - 15% overall. low LR rates with tumors < 2cm, but there is no correlation between size and LR.
 * distant mets - large size predicts metastatic spread. histologic type is prognostic. 10% DM rate overall, 20% in malignant lesions. LR does not predict DM.
 * regional spread - lymph node involvement in 10% overall

Disease free survival:
 * 96%, 74%, and 66% for benign, borderline, malignant tumors (Reinfuss et al)

Surgery:
 * Local recurrence is high with positive margins. Require wide local excision.  For benign lesions that were suspected to be fibroadenomas and excised without wide margins, a watch and wait approach is feasible.  Borderline/malignant tumors should be re-excised if there are positive margins. Mastectomy has no benefit over breast conserving surgery, but mastectomy can be done when the cosmetic outcome of a lumpectomy would be poor due to a large tumor in a small breast.  No need for axillary dissection.

Local recurrence can be treated with additional surgery.

For metastatic disease, chemotherapy is palliative.

Chemotherapy may be used in malignant types, using similar agents to those used for sarcomas.

The role of radiotherapy is unclear.

Pathology:
 * Ward & Evans / MDACC; 1986 PMID 3019505 &mdash; "Cystosarcoma phyllodes. A clinicopathologic study of 26 cases." (Ward RM, Cancer. 1986 Nov 15;58(10):2282-9.)
 * 26 pts. Evaluated pathologic factors for correlation with outcome
 * Described "stromal overgrowth" associated with metastatic disease and cancer-related death.

Literature

 * Harvard; 2019 (2000-2015) PMID 31814215 -- "Local recurrence after breast-conserving therapy for phyllodes tumors: A 15-year retrospective review." (Cervoni GE, Breast J. 2019 Dec 9. doi: 10.1111/tbj.13707. [Epub ahead of print])
 * Retrospective. 69 patients (48 benign, 13 borderline, 8 malignant). Median F/U 5 years
 * Local recurrence: benign 4%, borderline 0%, malignant 38% (SS). None of patients who received RT had a recurrence.


 * Rare Cancer Network; 2008 (1971-2003) PMID 17931796 &mdash; "Phyllodes tumor of the breast." (Belkacemi Y, Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):492-500.)
 * Retrospective. 443 pts, international. 85% breast conservation, 15% mastectomy. 64% benign, 18% borderline, 18% malignant. Adjuvant RT in 9%. Median F/F 8.8 yrs.
 * Outcome: LR in 19%, DM in 3.4%. If benign 11%, borderline 29%, malignant 28%. Good prognostic factors include younger age, small size, benign vs borderline/malignant histology, &le; 5 mitoses, no atypia, no stromal overgrowth, no necrosis
 * For pts with borderline or malignant tumor: RT associated with decreased LR, and TM associated with improved results. Benign tumors have excellent outcome with surgery alone. Recurences salvaged 92% with total mastectomy.
 * Conclusion: for borderline/malignant tumors, TM better than BCS. Consider adjuvant RT based on histologic criteria.


 * City of Hope; 2008 (1964-2005) PMID 18234448 -- "Malignant phyllodes tumor of the breast: local control rates with surgery alone." (Pezner RD, Int J Radiat Oncol Biol Phys. 2008 Jul 1;71(3):710-3. Epub 2008 Jan 30.)
 * Retrospective. Review of IMPAC National Oncology Database. 478 patients with malignant phyllodes tumor, from 130 hospitals. No RT given. Median F/U 5.3 years
 * Outcome: 5-year LC lumpectomy 79%, mastectomy 91%.
 * LC By size: lumpectomy <2 cm 91%, 2-5 cm 85%, >5cm 59%; mastectomy 100%, 95%, 5-10 cm 88%, 10-20 cm 85%
 * Conclusion: Adjuvant RT should be offered for tumors >2 cm treated with lumpectomy, and >10 cm treated with mastectomy


 * SEER; 2006 (1983-2002) PMID 16998937 &mdash; "Malignant phyllodes tumor of the female breast: association of primary therapy with cause-specific survival from the Surveillance, Epidemiology, and End Results (SEER) program." (Macdonald OK, Cancer. 2006 Nov 1;107(9):2127-33.)
 * 821 pts. Median f/u 5.7 yrs. Cause-specific survival of 91%, 89%, 89% at 5/10/15 yrs. Mastectomy in 52%, breast conservation (BCS) in 48%.
 * BCS associated with improved CSS. Adjuvant RT associated with decreased CSS.
 * Conclusion: mastectomy was not found to provide a benefit in CSS. The role of adjuvant RT is uncertain.


 * MD Anderson; 2002 PMID 11013364 -- "Primary treatment of cystosarcoma phyllodes of the breast." (Chaney AW, Cancer. 2000 Oct 1;89(7):1502-11.)
 * Retrospective. 101 patients (benign 58%, indeterminate 12%, malignant 30%). Stromal overgrowth 29%. Surgery lumpectomy 47% or mastectomy 53%. SM- in 99%, RT in 6%
 * Outcome: 10-year LC 8%, DM 13%. 10-year OS benign 79% vs. malignant 42%
 * Conclusion: Local failure low, if adequately resected disease, don't need adjuvant RT. If stromal overgrowth, chance of distant failure and should consider chemotherapy

Review

 * England (2001) - PMID 11423590 Full Text &mdash; "Phyllodes tumours." (Parker SJ, Postgrad Med J. 2001 Jul;77(909):428-35.)