Dec 20, 2020
This multi-institutional study highlights the heterogeneity of Phyllodes tumors of the breast and the importance of accurate pathology assessment and individualized surgical approaches.
LEE WILKE: This JCO podcast provides observations and commentary on the JCO article, Contemporary Multi-institutional Cohort of 550 Cases of Phyllodes Tumors from 2007 to 2017 Demonstrates a Need For More Individualized Margin Guidelines by Rosenberger, et al. My name Lee Wilke and I am a professor of surgery and the Hendrix chair in breast surgery research at the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin. My oncologist specialty is breast surgical oncology. I have no relationships to disclose related to these studies.
As medical students we are asked to adopt an expanded vocabulary to
describe a multitude of diseases. The word phyllodes is frequently
one of those memorable medical school terms whose origin is Greek
and describes a leaf-like growth. Phyllodes are rare tumors
accounting for less than 1% of breast malignancies, with just over
2,000 patients diagnosed annually in the United States.
Originally, the phyllodes tumor was described as cyst like and,
therefore, the historic term cystosarcoma phyllodes was applied.
Though these tumors are of connective tissue and fibroepithelial
origin, they are infrequently cystic and not a true sarcoma. And
therefore, the World Health Organization now classifies them as
simply phyllodes tumors. They are importantly, for treatment
approaches, sub-categorized into benign, borderline, and malignant
based on detailed pathologic review of celularity, atypia,
overgrowth, mitotic rate, and the borders of the tumor.
Phyllodes tumors are listed in the National Institute of Health's
genetic and rare diseases program. On the center's website, surgery
is described as the primary treatment for these rare malignancies
and 1 centimeter margins or greater are recommended for all
subtypes of phyllodes tumors, with a note that these tumors are
quote, "often treated with mastectomy", unquote. As specialists
caring for patients with breast malignancies, we are rapidly
learning that the one-size-fits-all approach is not appropriate,
and the same is true for those individuals with phyllodes
tumors.
In the article that accompanies this podcast, to support a shift
towards more individualized treatment, Dr. Laura Rosenberger from
Duke University in North Carolina assembled a group of key
collaborators from 11 US academic cancer centers to pool and
evaluate their treatment approaches and outcomes for patients with
phyllodes tumors. The investigators identified a total cohort of
550 patients with phyllodes tumors treated between 2007 and
2017.
Consistent with systematic reviews of phyllodes tumor data sets,
such as that by Lu et al in Annals of Surgical Oncology, with this
JCO publication being the largest, the patients have a median age
of 44. The malignant cohort is approximately 10%. And median tumor
size is three centimeters, with a range to as high as 29
centimeters. Key facts found within this analysis are that 2% of
patients underwent nodal evaluation, all with negative nodes.
The addition of either a sentinel node or axillary surgery is not
without risks to the patient. And unless the pre-surgical diagnosis
raises the question of a simultaneous adenocarcinoma, patients
undergoing surgery for a phyllodes tumor should not undergo nodal
mapping or axillary surgery as these tumors are primarily local
malignancies and do not metastasize via the lymphatic network. This
is the first key takeaway from this paper, supporting the work of
others that nodal surgery in phyllodes tumors is unnecessary.
The second notable finding is the heterogeneity, even among
academic medical centers, regarding the surgical approach.
Approximately 38% of patients, or 209, proceeded to a second
surgical intervention. 51 of these patients, or nearly 10% of the
entire cohort, had negative margins at their first surgery. Of the
group that underwent a second surgery, only six patients, or 3% of
those proceeding to a second intervention, had residual
disease.
On the opposite end of the spectrum, of those patients with a
positive surgical margin, which was 42% of the entire group, 74, or
32% of those with positive margins, did not proceed with a second
surgery. These outcomes highlight that even among patients being
treated at centers that one would assume would function similarly,
patients could have everything from positive margins to additional
surgery in the setting of negative margins.
What is vital to note at this point, however, is that the
recurrence rate for this cohort was only 3.3% or 18 patients-- 15
with a local recurrence and three with a distant recurrence. The
recurrences were differentially associated with the phyllodes
subtypes, with 1.3% in benign, 5.6% in borderline, and 6.9% in
malignant phyllodes. In univariate logistic regression analysis,
however, margin status and margin width did not predict for a
recurrence and neither did type of surgery or patient age.
Clearly, a one centimeter margin for a phyllodes tumor is not
needed, just as we are likely finding is true for our
adenocarcinomas of the breast. The authors don't go so far as to
state that a positive margin is acceptable, but highlight the need
for a national registry to evaluate an individualized surgical
approach in this rare patient population.
A final and third key point from this retrospective but important
pooled patient analysis is the primary role the pathologist plays
in determining the patient outcome. As I frequently comment to my
cancer patients, the pathologist is the most important doctor you
never meet. In Dr. Rosenberger's analysis, factors that were
influential for local recurrence were all pathological variables--
grade, extent of atypia and overgrowth and tumor size.
Currently, there are no College of American Pathologists guidelines
for reporting phyllodes tumors. With this and other patient data
sets highlighting the importance of these pathologic factors in
patient outcomes, perhaps a standardization and education program
for identifying each of these key findings within a phyllodes tumor
should be developed. Without a good pathologist or team of
pathologists, oncologic surgeons lack the tools they need to advise
the patient on additional surgery and potentially adjuvant
therapy.
As the use of adjuvant therapy was small in this data set,
conclusions could not be provided for or against radiation therapy.
Thus, as with all rare tumors, a collaborative and team approach
with development of a national registry is needed across community
and academic institutions to standardize and evaluate the outcomes
for these patients with the eventual goal of providing a more
tailored treatment approach. This concludes this JCO podcast. Thank
you for listening.