Not long after I retired from clinical practice in 2010
Jonathan W. Pine, Jr, Senior Executive Editor, contacted me
about preparing a fourth edition of
Breast Pathology
. This
came as a shock as I had only recently recovered from the ef-
fort that produced the third edition and was adjusting to the
freedom conferred by retirement. Mr. Pine and I had a very
good working relationship in producing the third edition,
and being curious to learn what he had in mind, I walked
the short distance from my home to the offices of Wolters
Kluwer/Lippincott Williams & Wilkins in Philadelphia. As
a result of this and subsequent conversations, we arrived at
the plan that has given birth to this fourth edition.
After writing the initial edition and revising it twice
single-handedly, I am honored that my three colleagues
and their associates consented to do the heavy lifting that
has been necessary to bring this much-improved Fourth
Edition to completion. The book has benefitted greatly from
their many decades of experience in the diagnosis of mam-
mary pathology at three of the most prestigious American
academic medical centers that are international leaders in
the treatment of breast diseases: New York Presbyterian
Hospital/Weill Cornell Medical College, Memorial Hospital
for Cancer and Allied Diseases/Memorial Sloan-Kettering
Cancer Center, and Massachusetts General Hospital/
Harvard Medical School.
I have known Syed A. Hoda, MD, for 20 years and
worked closely with him for nearly a decade in the Breast
Pathology Consultation practice I established at New York
Presbyterian Hospital, with the support and encourage-
ment of Daniel M. Knowles, Chairman of Pathology and
Laboratory Medicine. I was very pleased that Syed agreed to
serve as Editor, taking responsibility for overseeing the proj-
ect and looking after the innumerable details involved in the
creation of a book of this scope. Not the least of these tasks
was the final stage of uploading the chapter manuscripts and
images as required by the publisher.
Drs. Hoda, Brogi, and Koerner each undertook the
revision of approximately one-third of the book, in some
instances with the assistance of their associates. While ad-
hering to the basic outline established in prior editions, each
chapter has been thoroughly updated to include the most
recent information available when the manuscript was com-
pleted, as reflected in the substantial number of 2010 to 2013
references cited. In addition to thorough and extensively
illustrated descriptions of the surgical pathology and cytol-
ogy of the breast, the reader will find comprehensive, de-
tailed overviews of the many clinical facets of breast disease,
including epidemiology, clinical presentation, diagnostic
imaging, molecular/genetic analysis, clinical management,
and prognosis. Many new pictures have been added, others
have been replaced, and all have been carefully adjusted to
enhance image quality. Chapter 40, titled “Lymphoid and
Hematopoietic Neoplasms of the Breast,” was completely
rewritten using contemporary diagnostic terminology by
Judith A. Ferry, MD, from Massachusetts General Hospital/
Harvard University.
In the Introduction to the third edition to this book,
I drew attention to the growing recognition that “altered
gene expression is fundamental to neoplastic processes” and
noted that “the devil is in the details” of how the exceedingly
complex system of gene actions becomes disrupted, resulting
in the phenotypic changes in cells and tissues employed by
pathologists for diagnosis and estimating prognosis. It has
become apparent that the situation is even more complex.
Some genotypic alterations are linked to specific neoplasms
with similar phenotypic appearances, such as the genetic
alterations that underlie the diminished or absent expression
of adhesion molecules like E-cadherin in lobular carcinoma
or the
ETV6
–
NTRK3
fusion gene that characterizes secretory
carcinoma. On the other hand, an increasing number of ge-
netic alterations of significance for prognosis and treatment,
not readily apparent in the histologic phenotype of neo-
plasms, are being discovered by gene expression profiling,
and this is leading to an appreciation of unique characteris-
tics of individual tumors that may render them susceptible to
personalized therapies aimed at these targets. Of particular
interest is the discovery that some of the genomic alterations
found in mammary carcinomas also occur in carcinomas
that arise in other organs such as the uterus and ovaries.
In view of the rapid advances being made in the study of
the molecular biology of breast carcinoma and the grow-
ing intersection of the resultant knowledge with diagnostic
pathology, it was deemed important to expand this book by
adding Chapter 45, titled “Molecular Classification and Test-
ing of Breast Carcinoma,” by Drs. Yun Wu and Aysegul A.
Sahin from the M. D. Anderson Cancer Center/University
of Texas. This chapter provides an introduction to molecular
classifications under investigation and predictive molecular
tests that are currently used in clinical practice. Data from
molecular studies relevant to specific entities can be found
in individual chapters. Additional comments about provoca-
tive concepts relating to the molecular classification of breast
carcinoma that have emerged as a result of gene expression
profiling are addressed in a section titled “Molecular versus
Morphology for the Classification of Breast Carcinoma:
Must It Be Either/Or” in the Introduction.
Histopathologic examination will continue to be the
primary basis for the diagnostic classification of mammary
lesions in the foreseeable future. Molecular advances used
in the past two decades to generate alternative classifica-
tions have contributed to defining selected prognostic and
therapeutic subgroups within the context of the standard
Pre face
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