The authors have declared that no competing interests exist.
Primary sarcomas of the breast are <0.1% of all malignant tumours of the breast. To date, there are 13 major breast sarcoma series in English literature. This study adds to these series characterizing primary breast sarcoma among Philippine patients.
All breast biopsies from the pathology records of the University of the Philippines-Philippine General Hospital (UP-PGH) were searched for breast sarcoma cases from January 2000 to December 2010. Metaplastic carcinomas and phyllodes tumors were excluded.
There were 52 patients (45 female, 7 male) ranging in age 25-83 years (median 46 years). Majority had lump, ten cases with pain. No history of previous cancer was given. No history of prior radiation was found. Histopathological diagnoses were spindle cell sarcoma (n=13), fibrosarcoma (n=6), liposarcoma (n=6), MPNST (n=5), stromal sarcoma (n=5), angiosarcoma (n=4), MFH (n=4), leiomyosarcoma (n=3), rhabdomyosarcoma (n=3), chondrosarcoma (n=2), and synovial sarcoma (n=1). Tumors were with grade 1 (n=18), grade 2 (n=8), and grade 3 (n=10). Necrosis was noted in 6 cases. Simple mastectomy was done in 19 cases (37%), MRM in 31 cases (59%), while 2 far advanced had no surgery (3%). None had adjuvant radiotherapy or chemotherapy. The duration of follow-up for 45 patients ranged from 1 – 117 months, excluding those who were lost to follow-up. All 15 deaths were due to progressive disease. Recurrences were observed in 9 patients. The disease-free survival (DFS) and overall survival (OS) was 73%and 75%, respectively. On multivariate analysis, DFS and OS were significantly correlated with size (HR=113.63; p=0.019 and HR=77.36; p=0.037), grade (HR=20.73 ; p=0.003andHR= 39.57; p= 0.004), and having a histology of angiosarcoma (HR=35.20 ; p=0.005and HR= 50.74; p=0.007), respectively.
Sarcoma remains an important clinical entity among primary breast cancers.
Primary breast sarcoma (PBS) is a malignant tumor arising from the mesenchymal tissue of the mammary gland.
PBS is an extremely rare and heterogeneous disease initially described in 1887.
Because this tumor is rare, the majority of publications are case reports or small series. This study contributes to the literature on this disease and characterizes the Filipino patient with primary breast sarcoma, excluding cystosarcoma phyllodes.
This retrospective cohort included all cases diagnosed pathologically with primary breast sarcoma at the University of the Philippines-Philippine General Hospital (UP-PGH) Department of Pathology from January 2000 to December 2010. Excluded were patients aged <19 years, and those with other primary or metastatic disease to the breast, carcinosarcoma, spindle cell carcinoma, metaplastic carcinoma, or cystosarcoma phyllodes.
Clinical charts and surgical notes were retrospectively reviewed and the following information were collected: age, gender, size of tumor, clinical presentation, duration of symptoms, history of radiation, type of surgery, local recurrences, systemic metastases, and survival data. Follow-up information was obtained from patient records, death certificates, and correspondence. The patients were searched actively from the three medical records section (Main Records Section, Medical Oncology Records Section and Surgical Oncology Records Section) of the UP-PGH. Addresses and contact numbers were noted and correspondence was attempted via phone calls and letters. For those patients with vague addresses, attempts were made to contact their local government to help the authors find the patients for more accurate survival data.
Patient characteristics, method of biopsy, type and extent of surgery, histopathology, forms of treatment given, and sites of metastases were determined.
Continuous variables were summarized as means, medians, and ranges while categorical variables presented as frequencies and proportions. Stata Statistics Data Analysis software version 12.0 was used to analyze data. Three years OS and DFS following diagnosis were estimated based on the Kaplan-Meier method. Associations between age, size, grade, margin status, surgery and survival were evaluated based on fitting Cox proportional hazards models. All calculated
A pre-approved protocol submitted to the Research Ethics Board (UPMREB) Review Panel was used in this study.
The histopathologic diagnoses of all breast biopsies sent to the Department of Pathology (
Characteristics | No. of Patients (n=52) | % |
Age, years | ||
Median | 46 | |
Range | 25-83 | |
Size, cm | ||
Median | 7.4 cm | |
Range | ||
< 5cm | 12 | 23 |
5-10cm | 21 | 41 |
> 10cm | 19 | 36 |
Gender | ||
Male | 7 | 13 |
Female | 45 | 87 |
M/F Ratio | 1:0.15 | |
Histologic types | ||
Spindle-cell sarcoma | 13 | 26 |
Fibrosarcoma | 6 | 12 |
Liposarcoma | 6 | 12 |
MPNST | 5 | 10 |
Stromal sarcoma | 5 | 10 |
Angiosarcoma | 4 | 7 |
MFH | 4 | 7 |
Leiomyosarcoma | 3 | 5 |
Rhabdomyosarcoma | 3 | 5 |
Chondrosarcoma | 2 | 4 |
Synovial sarcoma | 1 | 2 |
Tumor grade | ||
Grade 1 | 18 | 34 |
Grade 2 | 8 | 15 |
Grade 3 | 16 | 31 |
Not graded | 10 | 20 |
Initial treatment | ||
Simple Mastectomy Alone | 19 | 37 |
Modified Radical Mastectomy | 31 | 59 |
Plus adjuvant CT | None | None |
Palliative RT | None | None |
Palliative RT + CT | None | None |
*MPNST malignant peripheral nerve sheet tumor, MFH malignant fibrous histiocytoma, CT chemotherapy, RT radiotherapy.
The 45 women had age range 25-83 (mean 46 years, median 46). There were 7 male patients with age range 32-64 (mean 41 years, median 51). Majority had with a lump, ten cases had pain. One case presented as an incidental mammographic finding. No history of previous cancer was elicited in any of the patients. No history of prior radiation was found in any case.
None underwent radiotherapy or chemotherapy.
Gross pathological description was available for 15 cases. Seven tumors were described as well-circumscribed, eight as infiltrative. Histopathological diagnoses were spindle cell sarcoma (n=13), fibrosarcoma (n=6), liposarcoma (n=6), MPNST (n=5), stromal sarcoma (n=5), angiosarcoma (n=4), MFH (n=4), leiomyosarcoma (n=3), rhabdomyosarcoma (n=3), chondrosarcoma (n=2), and synovial sarcoma (n=1). Tumors were graded as grade 1 (n=18), grade 2 (n=8), and grade 3 (n=10). Necrosis was noted in 6 cases.
Simple mastectomy was done in 19 cases (37%), MRM in 31 cases (59%), while 2 far-advanced had no surgery (3%). One patient initially underwent wide excision but the margins were positive, so she had simple mastectomy subsequently with clean margins. Of the 19 patients who underwent simple mastectomy, all had clear margins. Majority of the tumors (58%) subjected to simple mastectomy were <5 cm. Of the 31 patients who underwent MRM, three had lymph node involvement and positive margins. Those with no available margin status in their pathology report were assumed to have negative margins.
Forty-five patients had follow-up data ranging from 1-117 months; the others were lost to follow-up. There were fifteen deaths, all tumor-related. All patients with initially unresectable tumors died of their disease. Recurrences were observed in 9 patients; one chest wall recurrence occurred after mastectomy. Distant metastases developed subsequently in 8 patients. Four patients metastatic on initial presentation died within less than a year.
The 1-, 2-, and 3-year overall survival (OS) for the whole population was 89%, 81% and 75%, respectively. Disease-free survival rates at 1, 2, and 3 years were 78 %, 73 %, and 73% respectively (
Prognostic factors for disease recurrence are shown in
Prognostic factors for mortality are shown in
Disease Free Survival (%) | Univariate Results | Multivariate Results | |||
HR |
|
HR |
|
||
Tumor Size | |||||
<5 cm | 78 | 1.00 | - | 1.00 | - |
5-10 cm | 86 | 0.75 | 0.783 | 17.07 | 0.100 |
>10 cm | 49 | 3.20 | 0.158 | 113.63 | 0.019 |
Grade | |||||
1 | 91 | 1.00 | - | 1.00 | - |
2 | 88 | 2.41 | 0.336 | 2.71 | 0.374 |
3 | 40 | 10.48 | 0.001 | 20.73 | 0.003 |
Margin Status | |||||
- | 77 | 1.00 | - | 1.00 | - |
+ | 67 | 1.81 | 0.575 | 1.04 | 0.972 |
Type of Surgery | |||||
SM | 75 | 1.00 | - | 1.00 | - |
MRM | 77 | 1.10 | 0.866 | 0.14 | 0.067 |
Age | |||||
>40 | 80 | 1.00 | - | 1.00 | - |
≤40 | 66 | 1.76 | 0.366 | 0.76 | 0.772 |
Histology | |||||
Others | 84 | 1.00 | - | 1.00 | - |
Angiosarcoma | 0 | 13.47 | <0.001 | 35.20 | 0.005 |
*SM simple mastectomy, MRM modified radical mastectomy
Overall Survival (%) | Univariate Results | Multivariate Results | |||
HR |
|
HR |
|
||
Tumor Size | |||||
<5 cm | 78 | 1.00 | - | 1.00 | - |
5-10 cm | 86 | 0.73 | 0.715 | 23.86 | 0.122 |
>10 cm | 44 | 3.65 | 0.122 | 77.36 | 0.037 |
Grade | |||||
1 | 91 | 1.00 | - | 1.00 | - |
2 | 88 | 4.03 | 0.097 | 7.19 | 0.139 |
3 | 32 | 18.64 | 0.001 | 39.57 | 0.004 |
Margin Status | |||||
- | 77 | 1.00 | - | 1.00 | - |
+ | 50 | 1.49 | 0.704 | 0.60 | 0.678 |
Type of Surgery | |||||
SM | 74 | - | - | - | - |
MRM | 77 | 1.08 | 0.901 | 0.32 | 0.207 |
Age | |||||
>40 | 79 | - | - | - | - |
≤40 | 63 | 1.71 | 0.387 | 0.61 | 0.613 |
Histology | |||||
Others | 84 | - | - | - | - |
Angiosarcoma | 0 | 11.03 | <0.001 | 50.74 | 0.007 |
*SM simple mastectomy, MRM modified radical mastectomy
Author | Median age(years) | Median size (cm) | Top Diagnosis | PrognosticFactors | |
Berg et al(1962) | 25/- | 48 | 6.0 | Liposarcoma, fibrosarcoma | Positive margins |
Oberman(1965) | 13/30 yrs | 56 | 7.1 | Fibrosarcoma, rhabdomyosarcoma, desmoid | Size, type of surgery |
Norris & Taylor(1968) | 32/- | 49 | 4.0 | Osteosarcoma, MFH, leiomyosarcoma | Size, contour, atypia, mitotic index |
Barnes &Pietruszka (1977) | 10/31 yrs | 51 | 6.3 | Fibrosarcoma, rhabdomyosarcoma. leiomyosarcoma | Tumour contour, atypia, mitosis |
Callery et al(1985) | 25/33 yrs | 54 | 4.0 | Fibrosarcoma, MFH, Leiomyosarcoma | - |
Stanley et al (1988) | 4/- | 61 | - | MFH, angiosarcoma | - |
Pollard et al(1990) | 25/81 yrs | 55.4 | 5.9 | MFH, leiomyosarcoma, fibrosarcoma | Type of surgery |
Johnstone et al(1993) | 10/12 yrs | 28 | - | Angiosarcoma, MFH, rhabdomyosarcoma | - |
Smola et al(1993) | 8/23 yrs | 56 | 12.8 | Chondrosarcoma, MFH, leiomyosarcoma | - |
Gutman et al(1994) | 60/51 yrs | 48 | 6.5 | Angiosarcoma, spindle cell sarcoma | Size, multifocal lesions, vascular/lymphatic/chest wall invasion |
North et al(1998) | 25/31 yrs | 55 | 6.0 | Angiosarcoma, spindle cell sarcoma, fibrosarcoma | Type of surgery |
Barrow et al(1999) | 59/43 yrs | 45 | - | Fibrosarcoma, angiosarcoma, osteosarcoma | Size, margin status, histology |
Zelek et al(2003) | 83/37 yrs | 47 | 6.5 | MFH, angiosarcoma, leiomyosarcoma | Grade, size |
Adem et al(2004) | 42/80 yrs | 40 | 5.7 | Fibrosarcoma, angiosarcoma, leiomyosarcoma |
The risk of developing breast sarcoma is largely unknown. Some authors showed a significant correlation between external beam radiation of the breast or chest wall and sarcoma.
Breast sarcoma is mostly diagnosed in patients who are in their 5th or 6th decade of life, and the UP-PGH data is comparable to the largest review done by Al-Benna
Primary breast sarcomas are as histologically heterogenous as non-breast tissue sarcomas.
Also, PBS should be distinguished from metaplastic carcinomas (carcinosarcomas) of the breast, which represent as various combinations of poorly differentiated ductal carcinoma with mesenchymal and squamous components. There are clinicians in literature who classify and manage them as a variant of ductal adenocarcinomas of the breast. Therefore, when facing a spindle cell neoplasm in an epithelial organ such as the breast, one should be careful in rendering the diagnosis of sarcoma. In this setting, immunohistochemistry using the right antibodies is a major contribution. Berg defined stromal sarcomas of the breast in 1962 as a group of mesenchymal malignant tumors with fibrous, myxoid and adipose components, excluding malignant cystosarcoma phyllodes and lymphomas.
However, series in the literature have included many different entities under the rubric of sarcomas such as cystosarcoma phyllodes andlymphosarcoma.
In this UP-PGH data, the most common histologies were spindle cell sarcoma, fibrosarcoma, and liposarcoma constituting 50% of the whole population. This was comparable with the study done by Berg
The current 2010 American Joint Committee on Cancer TNM system
The results from this UP-PGH study showed that the lung was the most common site of distant metastases (75%), followed by the liver (25%).
Metastases from breast sarcoma spread hematogenously, and typically to the lungs, bones, and liver. Lymph node metastases are rare. In most cases of lymph node metastasis, the histopathologic subtype carcinosarcoma should be ruled out. Breast skin and the nipple areola complex are rarely involved by breast sarcomas, but angiosarcomas may be associated with a bluish discoloration of the skin overlying the lesion.7,8,15
There is still no definitive consensus regarding the treatment of PBS, even if simple mastectomy without axillary dissection is still widely regarded as the gold standard,
According to the clinicopathologic series done at the Mayo Clinic, lymphatic spread is uncommon as shown by the absence of axillary lymph node metastasis in their cases, and therefore axillary node dissection is not necessary. When lymph node metastasis is present, the diagnosis of a metaplastic carcinoma should be considered even in the presence of a pure spindle cell neoplasm, or that the sarcoma is far advanced.
Tumor size seems to be the most frequently reliable prognostic factor in many of these series, as in breast carcinomas and soft tissue sarcomas.
Breast sarcomas are primarily non-epithelial malignancies that arise from the connective tissue within the breast. They can be primary or secondary, as a result of treatment (usually RT) from previous breast malignancies. They are histologically heterogeneous, thus definitive histologic diagnosis maybe difficult if not seen by an experienced pathologist. They are extremely aggressive and once not properly diagnosed or managed early, have poor prognosis. Due to its rarity, it is difficult to conduct a prospective study to establish a standard of care for patients with primary breast sarcoma.
This UP-PGH series is similar to other series done in US and Europe, with findings as follows: (1) the larger the size, the poorer the prognosis; (2) the higher the grade, the poorer the prognosis; (3) angiosarcoma as a histologic subtype is associated with poor outcomes; and (4) the lung and liver are the most common sites of metastases. These are not different from the natural behavior of soft tissue sarcomas from other parts of the body. Therefore, primary breast sarcomas should be managed as such.
In the diagnosis of primary breast sarcoma, core needle biopsy is the procedure of choice for definitive diagnosis. Appropriate diagnostics should be ordered for accurate staging. According to the NCCN guidelines, chest CT scan should be ordered for all and abdominopelvic CT scans should be considered for angiosarcoma. For angiosarcomas, given the possible catastrophic outcomes, they should be offered early on maximal treatment, and that is, surgery, chemotherapy, and radiotherapy.
Due to the rarity of this disease, a multidisciplinary approach is recommended to properly manage this particular subset of sarcomas. Histologic review by an experienced soft tissue pathologistis critical in making the diagnosis and determining the histologic subtype. If diagnosis is still doubtful, appropriate immunostaining should be applied.