Key words breast - breast cancer - ultrasound - biopsy
Schlüsselwörter Mamma - Mammakarzinom - Ultraschall - Biopsie
Introduction
Women have a 10 % risk of developing breast cancer at some stage in their life. This
makes breast cancer the most common type of cancer found in women and the most
common cause of death for women between the ages of 35 and 55 years. In Germany,
around 58 000 women develop breast cancer every year, and approximately 20 000 die
of it [1 ]. The treatment options and the characteristics
determining the choice of therapy in patients with primary advanced breast cancer
are becoming ever more varied. New targeted therapies combined with established
chemotherapies have expanded the range of options [2 ], [3 ], [4 ], [5 ], [6 ], [7 ], [8 ].
Both European treatment recommendations and the German interdisciplinary S3-Guideline
on the Diagnosis, Therapy and Follow-up of Breast Cancer [9 ] propose that at least 70 % of all breast lesions suspicious for
malignancy (BI-RADS™ 4/5) be verified histologically preoperatively – the target is
90 % of lesions [9 ], [10 ], [11 ], [12 ]. By
preoperatively investigating suspected malignant processes, the aim is to ensure
that only one surgical intervention will be necessary. In addition, all non-palpable
breast lesions should be marked prior to the actual surgical intervention (e.g.
ultrasound-guided wire marking) [9 ], [10 ], [11 ], [12 ], [13 ].
Therapy studies performed in recent years in a neoadjuvant setting have greatly
increased our understanding of the effectiveness of therapies and their impact on
long-term survival [14 ].
Given the abundance of data on neoadjuvant chemotherapies and the good correlation
with pathologic complete remission (pCR), the American Food and Drug Administration
(FDA) carried out a meta-analysis of approximately 12 000 patients, which included
contributions by German study groups [15 ]. The prognostic
relevance of pCR for recurrence-free survival (HR 0.48, p < 0.001) and overall
survival (HR 0.48, p < 0.001) was confirmed beyond doubt. It was found that there
were no significant differences between the various definitions of pCR (with or
without the inclusion of DCIS). As regards tumour biology, the study found that the
more aggressive and sensitive to chemotherapy the tumour was, the higher the
prognostic relevance of pCR.
However, the neoadjuvant therapy concept represents new challenges for breast
surgeons, radiologists and pathologists, as with pCR there is no target point for
preoperative, ultrasound-guided wire marking. This problem can be effectively solved
by placing marker clips at the site of the primary breast tumour during
ultrasound-guided core needle biopsy prior to neoadjuvant chemotherapy [16 ], [17 ], [18 ], [19 ].
Based on our own extensive experience [20 ], the aim of our
study was to evaluate the precision of a newly developed method of clip marking in
patients suspicious for breast cancer.
Material and Methods
Single-use breast biopsy system (HistoCore™)
A single-use breast biopsy system (HistoCore™; BIP™ Biomed. Instrumente &
Produkte GmbH, Germany) ([Fig. 1 ]) [20] was used,
together with a 12 gauge, 10 cm long needle with a notch length of 18 or 25 mm.
After careful disinfection of the skin and administration of a local anaesthetic
(10 ml), the single-use breast biopsy system (a combination of a coaxial cannula
[11 gauge] and a core needle [12 gauge]) was placed over the tumour focus, and
core needle biopsy was done under ultrasound control, with the biopsy performed
tangentially to the linear 13.0-MHz transducer. The needle length prior to and
after the intervention was documented in pictures and on video. Four or more
core needle biopsy specimens were obtained to obtain sufficient material for
histological diagnosis and molecular-genetic investigation. A clip was placed in
the puncture area directly above the coaxial needle (11 gauge), i.e. in the
middle of the tumorous lesion.
Fig. 1 a to d Single-use breast biopsy and clip marker system.
a Clip, made of three biocompatible nitinol wires with diameters
of 0.15 mm (memory metal) twisted together to form rings with a diameter of
2.5 mm. b Directly adapted, precise clip marker system (O-Twist
Marker™), (20 gauge) – our own new development without a spacer.
c Coaxial needle (11 gauge) precisely adapted to the single-use
breast biopsy system (HistoCore™). d Single-use breast biopsy system
(HistoCore™): 12 gauge needle, needle length: 10 cm, optional notch length:
18 or 25 mm.
Clip system (O-Twist Marker™)
The O-Twist Marker™ clip system (Biomed. Instrumente & Produkte GmbH [BIP™],
Germany) has been on the market since 2003 [21 ]; it
was modified by us in 2012 in cooperation with BIP™ by precisely adapting the
length of the stylet to the HistoCore™ single-use breast biopsy system ([Fig. 1 ]).
The O-Twist Marker™ consists of three biocompatible nitinol wires with diameters
of 0.15 mm (memory metal) twisted together to form rings with a diameter of
2.5 mm. Each ring is flattened and inserted into a 20-G cannula. The marker is
ejected from the cannula through the stylet into the breast tissue where it
assumes its pre-assigned ring shape again at body temperature.
After placing the marker clip, control ultrasound (2D, Acuson Antares, 13 MHz;
Siemens™) and tomosynthesis (Selenia Dimensions3D™; Hologic™) scans are carried
out, which include computer-aided detection or diagnosis (CAD™ [R2™]) [19 ], [22 ], to precisely
locate the marker clip.
Results
Technical development
Our innovation consisted of the precise adaptation of stylet length to the
HistoCore™ single-use breast biopsy system [20 ]
([Fig. 1 ]). Before, when using the O-Twist
Marker™ clip system [21 ] (placed directly through the
coaxial core needle for the biopsy), the notch length used during marker clip
placement had to be varied for every procedure, depending on the respective
length of the core needle, using a pre-fabricated sliding spacer fitted over the
stylet. This approach was imprecise, as it was not possible to precisely adjust
the fitted spacer using only the marking rings engraved at intervals of one
centimetre. Our new development now offers the possibility of placing a precise
marker clip for every core length without needing a spacer.
Ultrasound-guided core needle biopsy and clip marking
Between 10/2012 and 03/2013, a total of 50 patients were examined at the
University Breast Centre for suspicion of invasive breast cancer (BI-RADS™ 4/5)
with a minimum lesion diameter of 2 cm (range: 2.3–3.3 cm) based on
complementary breast diagnostics.
Findings were confirmed histologically in all 50 patients by ultrasound-guided
core needle biopsy ([Fig. 2 ]) using the HistoCore™
single-use breast biopsy system [20 ].
Fig. 2 Ultrasound-guided core needle biopsy of suspected breast
lesions carried out using the HistoCore™ single-use breast biopsy system.
The core needle is directly in the middle of the focal findings (arrows)
(ultrasound done with the 2D, Acuson Antares, 13 MHz; Siemens™).
In addition, intramammary marker clips were placed, using our newly developed
clip system based on the well-known O-Twist Marker™ system [21 ] ([Fig. 3 ]).
Fig. 3 Clip marking using the O-Twist Marker™ system during
ultrasound-guided core needle biopsy of a suspicious breast lesion. The core
needle is located directly in the lesion (arrows) after placement of the
clip marker (marking circle) (ultrasound done using the 2D, Acuson Antares,
13 MHz; Siemens™).
Ultrasound and tomosynthesis scan to control location of marker clips
Ultrasound and tomosynthesis scans including CAD™ [19 ], [22 ] were carried out after placement
of the marker clips to determine the precise location of the marker clips ([Figs. 3 ] and [4 ]).
Fig. 4 a and b Tomosynthesis scan (Selenia Dimensions3D™;
Hologic™) to control the location of the intramammary marker clip.
a With CAD™ (R2™) – image 11; marker clip, blurred (circle), located
directly in the centre of the lesion. b With CAD™ (R2™) – image 25;
marker clip, sharply delineated (circle), located directly in the centre of
the lesion; 3 areas of micro calcifications are marked (dotted lines) and
classified as benign.
In 45 of 50 patients (90 %), ultrasound found no dislocation of the marker clip;
in 5 patients (10 %) the maximum dislocation was 5 mm along the x-, y- or
z-axis.
Tomosynthesis scans demonstrated precise placement without dislocation of the
marker clip in 48 patients (96 %); 2 patients (4 %) had a maximum dislocation of
maximal 3 mm along the x-, y- or z-axis.
Discussion
Interventional biopsy systems play an important role in complementary breast
diagnostics and mammography screening (assessment). They help reduce the number of
unnecessary diagnostic open surgical procedures in patients with suspicion of breast
cancer (BI-RADS™ 4/5) and provide samples for the histological verification of
lesions prior to the actual curative intervention or prior to neoadjuvant
chemotherapy. The EUSOMA recommends reducing the number of second interventions and
carrying out breast-conserving surgery in at least 70 % (90 % would be desirable) of
all patients with breast cancer. This is only possible with the use of
interventional biopsy systems [1 ], [2 ], [3 ], [4 ], [5 ], [6 ], [7 ], [8 ], [9 ], [10 ], [11 ], [12 ], [13 ].
Moreover, the inverse correlation between the number of tumour cells and the interval
between biopsy and surgery suggests that displaced tumour cells do not survive.
Other studies have shown that the rate of local recurrence and the interval to
tumour recurrence does not differ between patients who had percutaneous core needle
biopsy to verify the diagnosis and patients who had a primary surgical intervention
[23 ], [24 ], [25 ], [26 ]. Today,
ultrasound-guided core needle biopsy is considered the standard approach for the
diagnostic work-up of unclear lesions. Several studies have additionally shown that
an identical or even higher degree of diagnostic certainty can be obtained with
ultrasound-guided core needle biopsy compared to open biopsies of palpable and
non-palpable findings, which have a false negative rate of between 0.3 und 8.2 %
[27 ], [28 ].
The advantages of ultrasound-guided core needle biopsy, which can be carried out with
little expenditure of time, are its limited invasiveness and the low costs involved
[29 ], [30 ]. Knowledge of
the tumourʼs histological characteristics allows better planning of surgical
operations, if surgery is required, and a more targeted intervention. This is
reflected in the lower rate of follow-up surgical interventions for incomplete
tumour removal [31 ]. Moreover, around 75–80 % of lesions
found on imaging are benign, meaning that unnecessary surgical interventions can be
avoided, provided that the assessment of the images obtained during scanning
corresponds to the histological assessment of the lesion [32 ].
Based on our extensive experience [20 ] and using an
established clip marker system [21 ], the goal of our
study was to determine the precision of a new development to optimise marker
placement after ultrasound-guided core needle biopsy in patients suspicious for
breast cancer (BI-RADS™ 4/5). Subsequently, ultrasound and tomosynthesis scans
including CAD™ (R2™) were done to monitor the precise location of the marker clips
prior to carrying out further oncological therapy.
Our results confirm that our innovation permits precise adaptation of the length of
the marker system used in the HistoCore™ single-use breast biopsy system.
Previously, when using the O-Twist Marker™ clip system (placed directly through the
coaxial core needle for the biopsy), the notch length used during marker clip
placement had to be varied for every procedure, depending on the respective length
of the core needle, using a pre-fabricated sliding spacer fitted over the stylet.
This approach was imprecise as it was not possible to precisely adjust the fitted
spacer using only the marking rings engraved at intervals of one centimetre. Our new
development now offers the possibility of placing a precise marker clip for every
core length without needing a spacer. This is particularly important prior to
planned neoadjuvant chemotherapy, as in patients with pCR it is not possible to find
a target point for preoperative ultrasound-guided wire marking [16 ], [17 ], [18 ], [19 ].
Our innovation, which combines a single-use breast biopsy needle with precise,
length-adapted markers clips placed directly through the coaxial needle, represents
a further improvement in oncological therapy.
The results of ultrasound and tomosynthesis scans to monitor the placement and
location of the marker clips confirm the precision of tomosynthesis.
