Erratum to: Modeling precision treatment of breast cancer

During the type-setting of the final version of the article [1] some of the additional files were swapped. The correct files are republished in this Erratum.The online version of the original article can be found under doi:10.1186/s13059-015-0658-5.     

Toward precision medicine of breast cancer

In this review, we report on breast cancer’s molecular features and on how high throughput technologies are helping in understanding the dynamics of tumorigenesis and cancer progression with the aim of developing precision medicine methods. We first address the current state of the art in breast cancer therapies and challenges in order to progress towards its cure. Then, we show how the interaction of high-throughput technologies with in silico modeling has led to set up useful inferences for promising strategies of target-specific therapies with low secondary effect incidence for patients. Finally, we discuss the challenge of pharmacogenetics in the clinical practice of cancer therapy. All these issues are explored within the context of precision medicine.     

Follow-up after breast cancer treatment

BackgroundBreast cancer (BC) is the most common malignancy in women. Due to improved detectability and modern methods of treatment, the number of breast cancer survivors is estimated at 6 million women globally and is still increasing. The follow-up (FU) visits carried out at the Greater Poland Cancer Centre were assessed for compliance with Polish Society of Clinical Oncology (PTOK) and European Society for Medical Oncology (ESMO) guidelines.Materials and MethodsThe database covered 484 women who were treated for breast cancer in the Greater Poland Cancer Centre in 2013. Of these, 233 attended FU visits for 5 years after completion of radical treatment and had no cancer relapse. The number of FU visits and the number and type of additional tests performed were analyzed.ResultsThe median number of FU visits over 5 years was 14, which is in line with the guidelines. 51.6% women had a mandatory annual mammography. A significant number of women had additional tests that are not recommended in the guidelines.ConclusionsThere is a need to educate both physicians and patients on the principles of FU check-ups.     

Complex treatment of inflammatory breast cancer

Inflammatory breast cancer represents 2-5% of all malignant breast lesions. Its rapid progression, the rather short medical history of the disease is unique and seems to be very typical. The combined modality treatment of inflammatory breast cancer is a special challenge for the medical oncologists. Preoperative chemotherapy is of great importance. After getting fair remission, surgery and radiotherapy should be delivered. With combined modality therapy the 5-year overall survival is about 50%. Knowing more pharmaco-genomic details on the disease and delivering new medicaments the effectiveness of the treatment will be further enhanced.     

Exemestane experience in breast cancer treatment

Exemestane is a very potent, orally active, selective and long-lasting steroidal irreversible inhibitor of aromatase. It is 150 times more potent than aminoglutethimide (AG) in inhibiting human placental aromatase (K_i of 4.3 and 671 nM, respectively). The compound is presently under phase III evaluation in Europe and the U.S.A. for the treatment of postmenopausal advanced breast cancer (ABC). Clinical pharmacology studies have been carried out with single doses ranging from 0.5 to 800 mg and repeated doses of up to 600 mg a day, in 132 postmenopausal healthy volunteers and in 185 post-menopausal women with ABC. Results obtained using a very specific and sensitive analytical method (high performance liquid chromatography—radioimmunoassay; HPLC—RIA) indicated that exemestane is extremely effective in inhibiting plasma estrogens levels. Estrogen inhibition is clearly evident at 5 mg a day and maximal suppression for E₂, E₁ and E₁S (>85%, >90% and>90%, respectively) is obtained at 10–25 mg a day. Data from non-controlled phase II studies involving more than 400 patients indicated a clear anti-tumour activity in postmenopausal ABC patients failing multiple hormonal treatments. In 62 patients progressing on AG (≥500 mg a day) exemestane treatment resulted in an objective response rate of approximately 24%; disease stabilization ≥24 weeks was observed in an additional 24% of cases. With regard to safety, although daily doses up to 600 mg were administered, the maximal tolerated dose was not achieved; reported symptoms were mainly related to the pharmacological action of the compound and were usually mild to moderate in severity, resulting in the discontinuation of therapy in less than 3% of cases. In conclusion, the available results suggest that exemestane treatment is associated with minimal toxicity, and may be of significant benefit for ABC women who have exhausted conventional therapy.     

Risk biomarker assessment for breast cancer progression: replication precision of nuclear morphometry.

Nuclear morphometry is a method for quantitative measurement of histopathologic changes in the appearance of stained cell nuclei. Numerous studies have indicated that these assessments may provide clinically relevant information related to the degree of progression and malignant potential of breast neoplasia. Nuclear features are derived from computerized analysis of digitized microscope images, and a quantitative Feulgen stain for DNA was used. Features analyzed included: (1) DNA content; (2) nuclear size and shape; and (3) texture features, describing spatial features of chromatin distribution. In this study replicated measurements are described on a series of 54 breast carcinoma specimens of differing pathologic grades. Duplicate measurements were performed using two serial sections, which were processed and analyzed separately. The value of a single feature measurement, the nuclear area profile, was shown to be the strongest indicator of progression. A quantitative nuclear grade was derived and shown to be strongly correlated with not only the pathologic nuclear grade, but also with tubule formation, mitotic grade, and with the overall histopathologic grade. Analysis of replication precision showed that the standard methods of the histopathology laboratory, if practiced in a uniform manner, are sufficient to ensure reproducibility of these assessments. We argue that nuclear morphometry provides a standardized and reproducible framework for quantitative pathologic assessments.