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Page 2 of 12 Adler et al. J Cancer Metastasis Treat 2019;5:45 I http://dx.doi.org/10.20517/2394-4722.2019.03

complications [2-4] . Until 2015 mean survival times of 27 months were described, actual studies report
mean survival times of 55 months with a 85% incidence of spinal metastases [2-15] . An increased need for
surgical treatment of complications related to spinal metastases is the consequence. Due to mortality and
morbidity rates related to metastatic breast cancer every surgical treatment should be considered carefully.
Well evaluated scoring systems (revised Tokuhashi-or Tomita score, revised Bauer score, Van-der-Linden-
score, Karnofsky index) help surgeons to individually chose optimal treatment methods and to predict life
expectancies in cancer patients. But these scores only differentiate between tumor entities whereas respective
tumor phenotypes are not taken into account [16-21] . With the turn of the millennium five different intrinsic
subtypes of breast cancer were reported by means of gene expression profiles [14-22] . Four phenotypes are
decisive in daily clinical routine: luminal A, luminal B, HER2-enriched and basal like/triple-negative. With
[23]
an accordance of 70%-80% these phenotypes are assessed with immunohistochemical pathologic markers
(e.g., ER, PgR, HER2, KI-67/grading) as standardized gene expression profiling is available with partial
[24]
coverage . In this article we describe the molecular parameters of metastatic breast cancer to predict
survival time more precisely and to adequately calculate surgical therapies.

ASSESSMENT OF PROGNOSIS
The development of oncologic treatment options in primary breast cancer (in particular medical therapy) led
to considerable improved survival rates in the last decade [2-9,12-15,25-27] . Immunohistochemical diagnostic tools
provide a sufficient molecular phenotyping in breast cancer [Table 1].

Visceral, skeletal or cervical spine metastases, surgical complications and advanced patient´s age are reported
[13]
with different data in literature and therefore are not recommended as negative predictors . In contrast,
unimodal postoperative therapies, a disease-free interval less than 24 months, a high number of axillary
lymph node metastases and progress after first-line therapy mark assured predictors of shorter survival [4,10,13] .
Furthermore, patients’ wishes and preferences, symptoms, biological age, intrinsic breast cancer subtype,
[4]
tumor burden (number of metastasized organs) and prior therapies have to be taken into account .

MOLECULAR PREDICTORS
Around the turn of the millennium, Sørlie und Perou [14,22] published fundamental studies to classify breast
cancer at the molecular level with relevance to clinical course of disease. As tumor-biological classifications
increasingly become more complex, modern oncologic diagnostic and therapy options interact with highly
specialized regulatory mechanisms of cells and cell cycles [8,28] . The actual breast cancer classification [Table 1]
is based on histopathological examinations of a biopsy from the breast. Classifying breast cancer [1-3,5-9,12-15]
by estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor 2 (HER-2)
and a proliferation marker (KI-67) is global standard [23,24,28-33] . With these molecular genetic parameters
breast cancer is differentiated into the four intrinsic phenotypes, which are clinically relevant [Table 1].
Hormone receptor status comprises the combination of ER and PgR status [3,8,12] . Furthermore, endocrine
responsive subtypes (Luminal A and-B), triple negative and HER-2 over expressing immunophenotypes are
differentiated [2,3,8,13,14,23] . Luminal-A and Luminal-B phenotypes are clinically distinguished by proliferation
rate (e.g., KI-67), grading or a multigen signature [2,3,5-9,15,24,30] .

The common classification is based on the ubiquitous availability of these diagnostic methods, which
enable comparable studies and therapy concepts. With regard to metastatic breast cancer mean survival
times of 60 months are reported in the current literature [4,10,34] in case of endocrine responsive phenotypes
(Luminal-A and-B) compared to 26 months until the year 2015 [2,3,35] . Compared to PGR positive (PgR+)
[3]
status, patients with PgR negative (PgR-) status have a 59% higher mortality risk . In patients with hormone
receptor negative (HR-) status the mean survival time is reduced by 11 months and mortality risk is 52%