Steven I. Hajdu’s research while affiliated with State of California and other places

During the period from 1942 to 1962, treatment attempts with single‐agent chemotherapy such as nitrogen mustard and urethan gained limited application. However, the groundbreaking success with aminopterin in the treatment of patients with pediatric acute leukemia and methotrexate in the treatment of gestational choriocarcinoma established single‐agent chemotherapy as a pioneering contribution to oncology. The landmark discovery that early‐stage Hodgkin disease is curable with radiation made radiotherapy into an essential specialty of oncology. Although radical surgical treatment dominated the field of surgery, the excision of localized cancers with or without adjuvant radiation emerged as new modality in therapy. Cytopathology and surgical pathology became new fields in medicine and pathologists became an integral part of the preoperative, intraoperative, and postoperative care of patients with cancer. The discovery of multiple new drugs demonstrated promising results and widened the field of oncology from the laboratory to the clinic. In the etiology of cancer, precancerous conditions were named and carcinoma of the lung was definitively linked to cigarette smoking. All things considered, the progress made between 1942 and 1962 came about through the dedicated work of many individuals. However, there were 7 distinguished pathfinders (2 pathologists, 1 pediatric pathologist–oncologist, 1 radiation therapist, 1 physician‐actuary, 1 gynecologist‐oncologist, and 1 chemist) who, despite their different backgrounds, interests, and sex, made groundbreaking contributions to oncology.

The fields of medicine and oncology made substantial progress between 1800 and 1885. The first half of this period was dominated by the spectacular progress in physiology, cytology, histology, histopathology, and diagnostic microscopy. In the second half of the period, advancements in surgical techniques, anesthesia, asepsis, and laboratory medicine, including bacteriology, chemistry, and biochemistry, led to the development of medical specialties, including surgical pathology and surgical oncology. Although wars, revolutions, and socioeconomic upheavals interrupted the daily life of the populace, distinguished artists, scientists, and physicians continued, against all odds, to advance their field of interest. Among the many eminent individuals, there were 7 renowned physicians (4 pathologists and 3 surgeons) who revolutionized medical and oncology thinking in ways that are still felt today. They were polyglots with formidable erudition, beloved teachers, and mentors, and are remembered eponymically for their contributions to oncology to this day. As a passing note, the 3 surgeons also were skillful microscopists. Cancer 2017. © 2017 American Cancer Society.

During the 3 centuries reviewed herein, all that was known regarding cancer was limited to Italy, France, Germany, and England. Practically nothing was written about cancer in the rest of the known world, including the newly discovered geographic areas in the Americas, Africa, and Australia. The 7 pioneer physicians considered in this review lived through some of the most turbulent geopolitical, social, and religious upheavals that Europe had experienced during the Renaissance. Despite their diverse social, political, and religious backgrounds and disparate personalities, they were united in their commitment to the advancement of medicine and oncology and to spreading knowledge through printed texts. Collectively, they established the groundwork for modern anatomy, physiology, chemistry, pathology, surgical oncology, and chemotherapy. It perhaps is noteworthy that 5 of the 7 physicians who contributed the most to the advancement of surgery and surgical oncology served in various wars as army surgeons. Considering everything together, the refusal of physicians of this epoch to use the microscope is a historical enigma. Cancer 2017. © 2017 American Cancer Society.

This commentary highlights the onset and progression of the diagnosis and treatment of cancer from ancient times to the 15th century. During the preparation of this synoptic review of the lives and contributions to oncology of 7 ancient physicians, it became clear that despite separation by centuries, ethnicity, and religion, they had many things in common. For example, with the exception of Chauliac, all were born into wealthy families, had an excellent education in the liberal arts and sciences, and were mentored by outstanding teachers. After they became physicians, they traveled extensively, were polyglots, were sponsored by influential individuals, had inquisitive minds, searched for the true nature of diseases, and were proud to share the results of their observations with others. Except for Galen, all of them were kind and well-mannered individuals. They cared with sincere dedication for the poor and those who had untreatable disease, including cancer. Although their understanding of cancer was limited, they were deeply concerned about the neglect and hopelessness of cancer patients. They were aware of their shortcomings in offering effective treatment beyond the surgical excision of early cancers. For advanced cancers, they had nothing to give beyond palliative care with herbals and minerals. All physicians who care for cancer patients owe these pioneer physicians, whatever their shortcomings, an inexpressible debt for their attempts to cure cancer. Cancer 2016. © 2016 American Cancer Society.

Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers. Fifty-three cases of non-high grade and 46 cases of high grade DCIS were selected, and representative sections from each case were stained with antibodies to these cytokeratin markers. High grade DCIS showed significantly higher rates of expression with stem and basal cell markers compared with non-high grade DCIS (p <0.05). The majority of DCIS, both high grade and non-high grade, expressed luminal cell markers (67% to 91%) and single type of cell origin marker (72% to 87%). High-grade DCIS more frequently co-expressed all three types of cell origin markers compared with non-high grade DCIS (p <0.05). In summary, a subset of high grade DCIS frequently rises from stem or/and basal cell populations; the subset is associated with poor prognosis in invasive breast carcinoma. Thus, these markers may be used to identify a potentially more aggressive subgroup of breast carcinoma at its pre-invasive stage (DCIS), and to manage it accordingly. Second, most DCIS express luminal cell markers, suggesting that malignant transformation occurs relatively late along the cell differentiation pathway, contrary to the traditional belief that most neoplasms arise from a more primitive stem cell population. Third, the majority of DCIS exclusively express one type of progenitor marker, indicating that in most incidences they may arise from a single progenitor population. Last, triple expression of all types of cell origin marker is frequently associated with high grade DCIS, suggesting that more complicated pathways are involved in these more aggressive lesions. Further studies are needed to delineate the relationships of cell origin markers in DCIS and invasive carcinoma to the clinical outcome.

AimsHistorically, nuclear staining of 10% of invasive tumor cells was used for ER positivity. In 2010, ASCO/CAP guidelines recommended the cut off value be changed to nuclear staining of 1%. This study will analyze the relationships between levels of ER expression and clinicopathological features and clinical outcomes, with an emphasis on the ER 1-10% subgroup. Methods and ResultsWe analyzed clinicopathological features in 5 subgroups based on ER expression levels in 1700 consecutive invasive breast cancer patients diagnosed and treated at our institution between 2000 and 2011. 24% of cases had ER expression <1%, 2% were ER1-10%, 5% were ER11-50%, 5% were ER51-70% and 64% were ER71-100%. We observed four subgroups of patient cohorts (ER <1%, ER1-10%, ER11-70% and ER71-100%) that were unique in Nottingham grade, nuclear grade, PR expression and disease-free survival. Of the 341 patients with follow-up data, we found no significant differences in pathologic features between patients in the ER11-50% and ER51-70% subgroups. Conclusion These data support the important role of ER in breast cancer, and the importance of accurate testing and quantitative reporting for ER. Tumors with ER 1-10% are not common, and further studies are needed to better understand this subgroup of breast cancer.This article is protected by copyright. All rights reserved.

We have previously reported that high grade and non-high grade ductal carcinoma in situ (DCIS) of the breast can be subdivided into 3 cell origin subtypes (luminal, basal/stem, and null), and that high grade DCIS is more frequently associated with basal/stem cell subtypes compared to non-high grade DCIS. Here we refine the relationships between these 3 subtypes and the expression patterns of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (ERFR) in 53 cases of non-high grade and 46 cases of high nuclear grade DCIS. Using a panel of antibodies to ER-alpha, PR, HER-2/neu, and EGFR, along with cytokeratin (CK) markers (CK5/6, CK8, CK14, CK17, and CK18), we found that all 3 cell origin subtypes can express ER-alpha and PR, and their expression is higher in non-high grade DCIS than in high grade DCIS; the expression of HER-2/neu is associated with luminal subtype only in non-high grade DCIS, but can be seen in all 3 subtypes in high grade DCIS; the expression of EGFR is low and is present only in luminal cell subtypes in both high and non-high grade DCIS. Basal/ stem cell and null cell subtypes occur in younger patients in non-high grade DCIS compared to high grade DCIS. In conclusion, the expression patterns of ER-alpha, PR, HER-2/neu, and EGFR are markedly different in different cell origin subtypes of both high grade and non-high grade DCIS, suggesting that cell origin subtypes as well as nuclear grade contribute to the biological and molecular heterogeneity of DCIS.