Key words early breast cancer - adjuvant therapy - neoadjuvant therapy - St. Gallen panel of
experts
Introduction
In the last couple of decades, there has been a significant improvement in the treatment
and early detection of breast cancer. In addition to the introduction of new therapies,
a structural improvement in patient care has also largely been responsible for improving
the prognosis. Therapeutic recommendations, guidelines, participation in studies and
certification processes can be named in this connection [1 ], [2 ], [3 ], [4 ], [5 ], [6 ], [7 ]. A better prognosis or better therapeutic efficacy has been able to be demonstrated
for guideline-compliant treatment [3 ], treatment at certified breast centres [7 ] as well as for patients with study participation [4 ], [6 ]. In view of this, it is of particular importance that, in an interdisciplinary framework,
therapeutic recommendations are revised again and again, studies are reinterpreted,
and the results of this discussion are disseminated. The current therapeutic recommendations
of the German committee for the treatment of breast cancer patients (AGO-Mamma) were
only recently published [8 ] and the S3 guidelines were most recently updated in December 2017 [1 ], [2 ]. On the international level, the St. Gallen conference, in which views and experiences
are exchanged every two years and current issues are discussed and voted on, is of
particular importance for the international exchange of interpretations of medical
issues with regard to early, non-metastatic and thus curative breast cancer. In view
of the therapeutic recommendations mentioned and the St. Gallen conference, current
aspects of clinical breast cancer research for patients with early breast cancer will
be presented in this overview. The votes published here, which reflect the opinion
of international experts, do not always comply with national therapeutic recommendations
and guidelines. For a discussion of the voting results in view of German therapeutic
recommendations and guidelines, we refer to Untch et al.
Genetic Testing for Germ Line Mutations
Genetic Testing for Germ Line Mutations
It is known that a significant proportion of the familial breast cancer risk is caused
by mutations in high- and moderate-penetrance genes and genetic variants in low-penetrance
genes. While until recently, only BRCA1 and BRCA2 were considered when testing for germ line mutations, the role of so-called panel
genes has become better understood in recent years [9 ], [10 ], [11 ], [12 ]. In addition, considerable efforts have been made in studies with more than 400 000
patients in order to be able to validate the low-penetrance variants. In [Fig. 1 ], the timelines and the known contribution of the genetic mutations and variants
in each case are described [13 ], [14 ], [15 ], [16 ], [17 ], [18 ], [19 ]. While BRCA1 and BRCA2 are responsible for approx. 16% of the twice-as-high familial breast cancer risk,
another 4% can be explained by the panel genes (such as PALB2, CHEK2, BARD1 ) and others. To date, over 170 common and low-penetrance gene loci have been described
which explain another 18% of the breast cancer risk [13 ], [14 ], [15 ], [16 ], [17 ], [18 ], [19 ]. Thus somewhat less than 40% of the twice-as-high familial breast cancer risk can
be explained by genetic changes. Molecular subtypes and other risk factors such as
the mammographic density are increasingly also integrated In the risk calculations
[11 ], [13 ], [20 ], [21 ], [22 ], [23 ], [24 ], [25 ], [26 ].
Fig. 1 Explainability of the twice-as-high familial risk by breast cancer risk genes (high-penetrance
genes, moderate-penetrance genes and low-penetrance variants, according to [13 ], [14 ], [15 ], [16 ], [17 ], [18 ]).
While most germ line changes which have been associated with breast cancer have no
systemic therapeutic consequence, efficacy of the PARP inhibitors olaparib and talazoparib
was established for HER2-negative patients with advanced breast cancer and a germ
line mutation in BRCA1 or BRCA2
[27 ], [28 ]. Studies in the neoadjuvant or adjuvant therapy of early breast cancer are being
performed and they are still waiting to be published. In early breast cancer patients,
it is known that patients with a BRCA1/ 2 mutation in the case of neoadjuvant chemotherapy have a greater chance of a pCR
[19 ], [29 ], [30 ]. Likewise there is evidence that women with a BRCA1/2 mutation have a somewhat better
prognosis following chemotherapy than patients without a mutation [29 ], [31 ].
General questions on genetic testing were voted on by the St. Gallen panel (StGP).
In patients with early breast cancer, the experts appeared to orient themselves on
the recommendations for predictive genetic diagnostics. The results are summarised
in [Table 1 ]. In view of a therapeutic option for metastatic patients with triple-negative disease,
a clearer positioning of the panel in favour of testing of all patients with TNBC
would have been desirable here. However, the panel oriented itself on the expected
mutation rates and therefore issued only a strong recommendation for testing patients
with TNBC under the age of 60. In Germany, this results in a window of 10 years, between
age 50 and 60, in which testing is recommended but is not covered by health insurance.
Table 1 Vote on the indication of high-penetrance germ line mutations. There were 53 voting
experts; the number of those who did not vote is not known.)
High risk germline mutations
Genetic testing for high risk mutations after counselling should be considered in:
All women with breast cancer:
29.2%
70.8%
0%
Patients with a strong family history:
100%
0%
0%
Patients under 35 at diagnosis:
95.9%
4.1%
0%
Patients under 50 at diagnosis:
32.7%
65.3%
2%
Patients under 60 with TNBC:
85.4%
14.6%
0%
Patients with TNBC at any age:
38.8%
59.2%
2%
Local Therapy – Surgery and Radiation Therapy Can Still Be Optimised
Local Therapy – Surgery and Radiation Therapy Can Still Be Optimised
Historically, the local treatment of breast cancer has been characterised by a markedly
aggressive approach [32 ], [33 ]. However, the introduction of concepts which connect radiation therapy and surgery
have decisively shaped the local treatment of breast cancer, as the introduction of
breast-conserving therapy has shown [34 ], [35 ]. Unlike almost no other therapeutic method, attempts are made in the case of local
therapy to continuously minimise the intervention in order to reduce long-term consequences
as much as possible while preserving oncological security. A series of votes by the
StGP also determined this basic principle.
Even if the radicality of the axilla surgery has already been significantly reduced
through the introduction of sentinel lymph node removal, knowledge on the prognosis
of some patient groups now already indicates that in some cases, the axillary surgery
can be completely eliminated. Whether this approach is acceptable in the case of patients
with clinically unremarkable axilla and negative axillary ultrasound is currently
being clarified in three clinical studies [36 ], [37 ], [38 ].
A whole series of studies addressed the question of what is the best approach in the
case of a positive sentinel lymph node. Several studies (IBCSG 23-01, AMAROS, ACOSG
Z0011) were able to show for patients with breast-conserving therapy and subsequent
radiation that, under certain conditions, complete axillary lymphadenectomy in the
case of positive sentinel lymph nodes can be eliminated [39 ], [40 ], [41 ], [42 ], [43 ]. There are considerably fewer data in the case of patients with positive SNL following
mastectomy, even if the IBSCG 23-01 and the AMAROS study admitted patients with mastectomy.
Knowledge regarding the safety of this approach following neoadjuvant chemotherapy
is likewise limited. In view of these data, the experts of the StG panel voted on
several questions in this connection ([Table 2 ]).
Table 2 Vote regarding the coordination between axillary surgery and radiation. There were
53 voting experts; the number of those who did not vote is not known.)
Radiotherapy approach in patients with macrometastatic SLN that did not undergo ALND
In a patient with a tumour below 5 cm and 1 – 2 positive SLNs that has undergone a
breast conserving procedure and is scheduled for whole breast irradiation (“Z11 criteria”):
41.70%
29.20%
25%
4.20%
Surgery of the Axilla: postmastectomy
Based on e.g. the AMAROS trial and other data sets, the preferred approach for women
with T1–2 cancers undergoing mastectomy and SLN mapping with macro-metastases in 1 – 2
sentinel nodes should be (assuming standard systemic adjuvant therapy):
12.50%
16.70%
47.90%
8.30%
14.60%
ALND in patients with macrometastatic SLN
ALND can be omitted in:
ALND can be omitted in mastectomy with 1 – 2 positive SNs, TNBC and RNI planned:
70.80%
22.90%
6.20%
ALND can be omitted in mastectomy with 1 – 2 positive SNs and chest wall but not RNI
planned:
19.10%
66%
14.90%
ALND can be omitted in mastectomy with 1 – 2 positive SNs, ER+ and HER2+, and RNI
planned:
83.30%
8.30%
8.30%
ALND can be omitted in patients with tumours > 5 cm undergoing BCT with 1 – 2 positive
SNs and undergoing WBI:
34.80%
60.90%
4.30%
ALND can be omitted in patients with tumours > 5 cm undergoing BCT with 1 – 2 positive
SNs and undergoing WBI breast and nodal radiation planned:
73.90%
21.70%
4.30%
Mastectomy with 3 positive nodes out of 3 removed and planned RNI:
not available
not available
not available
Use of SLND in cN1 undergoing PST
In a patient who is clinically node positive (cN1) at presentation and downstages
to cN0 after neoadjuvant therapy, SLN can substitute for ALND if:
1 – 2 negative SLNs obtained:
54.20%
43.80%
2.10%
3 or more negative SLNs obtained:
91.70%
4.20%
4.20%
A clipped (marked) node, with or without additional SLNs is removed and is negative:
43.80%
43.80%
12.50%
A clipped (marked) node, with additional SLNs is removed and is negative:
92.10%
5.30%
2.30%
ALND after PST when there is residual axillary disease
In a patient who is cN1 at presentation and has a good clinical response; SLN mapping
identifies 3 SLN:
ALND may be avoided if there is limited involvement with micrometastasis in one positive
node only (no radiotherapy planned):
25.50%
63.80%
10.60%
There are only very few data on the question of resection margins, particularly in
the case of concomitant DCIS. Here the assessments of the panel of experts are helpful
and may help avoid subsequent resection.
Other questions which the StGP addressed include the indication for radiation following
mastectomy, hypofractionated radiation, the integration of oncoplastic surgeries and
regional lymph node irradiation (RNI). All of the questions and answers can be found
in the supplement Table S1 .
Chemotherapy or No Chemotherapy – Determination of Molecular Markers and Multigene
Expression Tests
Chemotherapy or No Chemotherapy – Determination of Molecular Markers and Multigene
Expression Tests
While the indication for patients with TNBC and HER2-positive tumours is relatively
clearly regulated by the guidelines and therapeutic recommendations, the question
often arises in routine clinical practice as to which patients with HR-positive, HER2-negative
breast cancer should be treated with adjuvant or neoadjuvant chemotherapy. It is clear
that there are tumours in this group of patients which do not respond well to chemotherapy
[44 ], [45 ], [46 ]. It is also known that some patients in this group have an extremely good prognosis.
Given this, there is the question of the extent to which multigene tests can help
in making a decision. For two multigene tests, there are studies which have attempted
to include the use of their prognostic significance in therapy algorithms [47 ], [48 ]. Both studies were able to identify patient collectives whose prognosis was sufficiently
good that the benefit of chemotherapy could not be proven or it was questionable whether
chemotherapy was necessary. The use of chemotherapy in breast cancer patients has
significantly decreased in recent years [49 ]. Part of this decrease was attributed in a U. S. study on node-positive patients
to the use of multigene tests, even if the largest proportion of the decrease in the
use of chemotherapy could not be explained by the decision-making aid of a multigene
test [49 ]. The vote regarding some clinically relevant questions is summarised in [Table 3 ].
Table 3 Votes relating to multigene tests. There were 53 voting experts; the number of those
who did not vote is not known.)
Multigene signatures and chemotherapy decision making in ER+ HER2− tumours
In T1/T2, N0 cancers, genomic assays are valuable for determining whether to recommend
chemotherapy?
93.60%
4.30%
2.10%
In T3 NO cancers, genomic assays are valuable for determining whether to recommend
chemotherapy:
74.50%
21.30%
4.30%
In T any (1 – 3+ LN), genomic assays are valuable for determining whether to recommend
chemotherapy?
78.70%
17%
4.30%
TAILORx and beyond: recurrence scores ≤ 25
The 21-gene recurrence score, if available, is widely used to assist adjuvant chemotherapy
decisions, and that based on TAILORx, women with node-negative cancers and recurrence
scores ≤ 25 do not need chemotherapy
Women of age < 50 with node negative cancer and RS 21 – 25 should receive:
41.70%
25%
10.40%
16.70%
6.20%
Postmenopausal women with node-negative cancers and RS ≥ 26
Postmenopausal women with node-negative cancers and RS > 26 should be offered chemotherapy:
38.80%
57.10%
0%
4.10%
0%
Recurrence score in LN+ (PlanB trial)
RS < 11 or equivalent in women of age > 50 years and 1 – 2 positive LN may be used
to recommend against chemotherapy:
78.70%
14.90%
6.40%
Mammaprint in LN+ (based on MINDACT)
Mammaprint low in women of age > 50 years and 1 – 2 positive LN may be used to recommend
against the indication for adjuvant chemotherapy:
80.90%
12.80%
6.40%
Mammaprint in LN+ (based on MINDACT)
Mammaprint low in women of age < 50 years and 1 – 2 positive LN may be used to recommend
against the indication for adjuvant chemotherapy:
78.70%
19.10%
2.10%
Immunological Diagnostics in Early Breast Cancer
Immunological Diagnostics in Early Breast Cancer
In the metastatic therapy situation, efficacy has already been able to be demonstrated
for immunotherapy with the PD-L1 checkpoint inhibitor atezolizumab [50 ]. Triple-negative patients whose immune cells in the tumour demonstrated an expression
of PD-L1 had better progression-free survival and better overall survival in the case
of combination therapy consisting of nab-paclitaxel and atezolizumab, compared to
monotherapy with nab-paclitaxel [50 ]. In the case of patients with early breast cancer, therapy with chemotherapy (nab-paclitaxel
followed by epirubicin + cyclophosphamide) was compared in a phase II study with 174
patients to this chemotherapy + durvalumab. The study demonstrated an increase in
pCR from 44.2% with chemotherapy to 53.4% with chemotherapy + durvalumab. Given the
small number of cases, this difference was not statistically significant, however
[51 ]. Additional therapeutic data from immunotherapies are currently not yet known in
the case of early breast cancer. The situation is different with regard to the knowledge
gained on tumour-infiltrating lymphocytes (TILs). In a large pooled analysis, it could
be shown that TNBC and HER2 patients with high TIL values have a higher response rate
to conventional, neoadjuvant chemotherapy and are also associated with a better outcome.
In the case of HER2-negative, hormone-receptor-positive patients, this connection
is still controversial [52 ]. In other studies as well, the connection between TILs with the response to neoadjuvant
chemotherapy was able to be shown [53 ], [54 ], [55 ]. In some studies in the adjuvant therapy situation, a prognostic effect was likewise
able to be shown [56 ].
[Table 4 ] summarises the assessments of the StGP with regard to an integration of TIL determinations
and PD-L1 determination in the case of TNBC patients in routine clinical practice.
In these votes, it is interesting to note that 66% of the panel members were of the
opinion that TILs should be measured in routine clinical practice, however in the
following questions, the vast majority clearly rejected a clinical benefit in routine
practice.
Table 4 Votes on immunological-pathological diagnostic measures in TNBC. There were 53 voting
experts; the number of those who did not vote is not known.)
Pathology: TNBC only
TILs should routinely be characterized and reported according to consensus criteria:
66%
34%
0%
TILs should be characterized because tumours with high TILs do not need chemotherapy?
6.10%
89.80%
4.10%
Do you obtain TILs in your daily practice?
25.50%
70.20%
4.30%
TILs should be characterized because tumours with high TILs may need less chemotherapy?
11.40%
79.50%
9.10%
Tumour PDL1 expression should routinely be reported:
20.80%
79.20%
0%
Immune cell PDL1 expression should routinely be reported:
8.50%
91.50%
0%
Adjuvant Endocrine Therapy – Optimisation Still Underway
Adjuvant Endocrine Therapy – Optimisation Still Underway
While there is no doubt that all patients without contraindications and with a response
to antiendocrine therapy should receive such therapy, several questions are still
being discussed.
For nearly two decades now, attention has been paid to the question of the cut-off
of positively stained cells in immunohistochemistry [57 ], [58 ], [59 ], [60 ], [61 ], [62 ], [63 ]. This also appears to still be a question amongst clinicians ([Table 5 ]).
Table 5 Votes (excerpt) in connection with adjuvant antihormonal therapy. There were 53 voting
experts; the number of those who did not vote is not known.)
Endocrine therapy
Ideal cut off to prescribe endocrine therapy:
30.60%
4.10%
38.80%
24.50%
2%
Endocrine therapy – Premenopausal: selection factors
Clinico-pathological indications for ovarian function suppression (OFS) are:
Those given chemotherapy:
68.10%
25.50%
6.40%
Clinico-pathological indications by itself for ovarian function suppression (OFS)
include:
Age ≤ 35 years
84.80%
8.70%
6.50%
Moderate risk not getting chemotherapy
45.80%
41.70%
12.50%
Premenopausal E2 level after (neo)adjuvant chemotherapy
not available
not available
not available
Involvement of how many nodes?
37.80%
13.30%
17.80%
31.10%
Adverse result of multi-gene test
59.60%
23.40%
17%
HER2+ status
33.30%
52.10%
14.60%
Endocrine therapy – Duration (postmenopausal) beyond 5 years
It is understood that 5 years of endocrine therapy is a historic standard, and that
only patients who have tolerated such treatment reasonably well would discuss longer
durations of therapy. Would you recommend extended therapy for:
Stage 1, after 5 years tamoxifen?
25.50%
72.30%
2.10%
Stage 1, after 5 years of an AI?
19.60%
78.30%
2.20%
Stage 2, node-negative, after 5 years of tamoxifen?
68.10%
27.70%
4.30%
Stage 2, node-negative, after 5 years of an AI?
34.70%
59.20%
6.10%
Stage 2, node-positive, after 5 years of tamoxifen?
97.90%
2.10%
0%
Stage 2, node-positive, after 5 years of an AI?
81.20%
12.50%
6.20%
Patients receiving extended endocrine therapy should aim for a total treatment duration
of:
58.50%
31.70%
9.80%
Patients at very high risk (e.g. 10 or more positive nodes) should receive endocrine
therapy beyond 10 years
14.60%
22.90%
60.40%
2.10%
Another important and frequently discussed subject area is the implementation of optimal
antiendocrine therapy in patients in premenopause. In the SOFT and TEXT studies, it
was able to be shown that ovarian function suppression (OFS) demonstrated an advantage
for disease-free survival when this was combined with therapy with tamoxifen or the
aromatase inhibitor exemestane [64 ]. Patients with exemestane and OFS or tamoxifen and OFS had better disease-free survival
than patients with tamoxifen monotherapy. In a comparison of tamoxifen + OFS and exemestane
+ OFS, it was also seen that therapy with exemestane + OFS demonstrated better disease-free
survival. For a better understanding of the data to which these data refer, see [Fig. 2 ]. The results for overall survival were not significant in all comparisons and in
all subgroups. It should also be noted that the adverse effects on OFS were higher
than in the case of monotherapy with tamoxifen. In view of this, the StGP voted on
a series of questions dealing with the issue of which patients should receive OFS
and for how long ([Table 5 ]). While there was no consensus for some questions, it can be relatively clearly
induced from the responses that the panel favours the use of OFS in patients under
age 35 who have received chemotherapy.
Fig. 2 Design of the analysis of the SOFT and TEXT studies (according to [64 ]).
With regard to the antiendocrine treatment of postmenopausal patients, aromatase inhibitors
had already become established more than 10 years ago in various therapies containing
an aromatase inhibitor. These therapeutic concepts contained the administration of
aromatase inhibitors alone or the start of therapy with tamoxifen and then a switch
to an aromatase inhibitor. This gives rise to questions relating to the duration of
therapy and whether and for how long a sequence of tamoxifen and aromatase inhibitors
can be used ([Table 5 ]). What is particularly interesting about the results is the fact that the panel
bases the decision for expanded therapy significantly on tumour stages and, for example,
does not recommend any expanded therapy in stage I even after 5 years of tamoxifen.
Chemotherapy in Neoadjuvant, Adjuvant and Post-Neoadjuvant Situations
Chemotherapy in Neoadjuvant, Adjuvant and Post-Neoadjuvant Situations
While the introduction of chemotherapy in the treatment of breast cancer as well as
the introduction of anthracyclines and taxanes has primarily taken place via classical
and, to some extent, very large adjuvant studies, further insights have been able
to be gained in recent years, particularly through the combination of knowledge regarding
the response to therapy in the neoadjuvant situation and its effects on the prognosis
[44 ], [46 ], regarding the patients in whom chemotherapy leads to a response to chemotherapy
and in whom this affects the prognosis. Particularly in the case of patients with
TNBC- or HER2-positive carcinoma, a clear connection was able to be established here
[44 ], [46 ].
Some questions which are currently being discussed are the use of anthracyclines,
the use of platinum derivatives, the type of chemotherapy (standard dose vs. dose-dense
dosing) and the chemotherapy combination partners within the scope of anti-HER2 therapies.
In a large randomised study, it was shown that in the case of adjuvant therapy with
trastuzumab, therapy with an anthracycline can be avoided if a platinum-based chemotherapy
is administered instead [65 ]. The benefit of avoiding anthracyclines is a reduction in their long-term cardiac
effects. In HER2-negative patients as well, it has been hypothesised that chemotherapy
containing anthracyclines can be avoided because it is known that a TOP2A amplification is not present in patients with a lack of HER2 amplification [66 ], [67 ], [68 ]. TOP2A is in turn one of the main points of attack of chemotherapy containing anthracyclines.
In fact, two German studies were able to confirm that anthracycline can be avoided
in HER2-negative patients [69 ], [70 ].
In the case of chemotherapies with dose-dense administration, the data in recent years
have also become concentrated such that it can be estimated for most groups of patients
whether and how they benefit from dose-dense chemotherapy [71 ]. The data are documented via a number of studies and meta-analyses performed [72 ]. The experts of the StGP voted on these questions as well.
Also of interest were the opinions on the use of platinum-based chemotherapy in triple-negative
patients. The background is that it is assumed that in patients with a triple-negative
tumour, DNA repair mechanisms are more frequently disrupted and therefore platinum-based
chemotherapies work better. In the neoadjuvant situation, there are solid data which
show that platinum-based chemotherapies increase the pCR rate, however this happens
at the cost of more frequent and more severe haematological toxicities [73 ]. With regard to the prognosis, the studies were not able to establish such a clear
connection [73 ]. The votes regarding chemotherapy are shown in [Table 6 ]. An interesting aspect shown by the international composition of the panel cannot
be seen from the voting results, however this was very clear during the discussion.
While in Germany the indication for neoadjuvant chemotherapy is largely based on the
tumour biology, the head of the panel, Eric Winer, clarified that in the USA, only
a minority of patients in stage I are treated neoadjuvantly and in these cases, adjuvant
chemotherapy is generally preferred.
Table 6 Votes (excerpt) regarding (neo)adjuvant chemotherapy. There were 53 voting experts;
the number of those who did not vote is not known.)
Preferred chemotherapy regimens in ER+ breast cancer in N-
The preferred chemo-regimen should be:
31.20%
54.20%
4.20%
10.40%
Chemotherapy in TNBC: anthracyclines
In women with stage 1 TNBC, the preferred chemotherapy regimen should be:
77.60%
16.30%
0%
6.10%
In women with stage 1 TNBC, the preferred chemotherapy regimen should be (in pT1a/b):
30.40%
52.20%
4.30%
13%
Women with stage 2 or 3 TNBC should receive which chemotherapy regimen:
93.30%
2.20%
0%
4.40%
TNBC chemotherapy: neoadjuvant platinum
Should a platinum-based regimen be recommended
In addition to T/C/A based regimens
34.80%
56.50%
8.70%
In patients with known BRCA mutation
67.30%
26.50%
6.10%
Chemotherapy in TNBC; tumour less than 6 mm N0
Should women with unifocal pT1a pN0 receive chemo?
0%
65.30%
34.70%
0%
Optimal chemotherapy schedule
When giving adjuvant/neoadjuvant chemotherapy with anthracycline and taxanes, the
preferred schedule is:
31.70%
61%
7.30%
HER2+ breast cancer
It is understood that standard management for HER2+ breast cancer includes chemotherapy
and trastuzumab, including patients with stage 1 tumours. Do the large majority of
patients with HER2 positive node-negative disease require anti-HER2 therapy:
With T1a disease?
42.60%
55.30%
2.10%
Does ER status affect any of these thresholds?
27.70%
61.70%
10.60%
The preferred regimen for stage 1 adjuvant, HER2+ is:
73.50%
4.10%
2%
12.20%
8.20%
HER2+ tumours: stage 2 (N+) or 3
The preferred adjuvant or neoadjuvant approach for stage 2 (N+) or stage 3, HER2 positive
breast cancer is:
14.30%
75.50%
0%
4.10%
6.10%
HER2+/ER+ tumours: stage 1
Pertuzumab is a standard when using trastuzumab with indication for neoadjuvant therapy:
33.30%
52.10%
14.60%
Pertuzumab should be added in:
12.80%
2.10%
25.50%
48.90%
10.60%
HER2+ preferred approaches stage 2 (N+) or 3
Pertuzumab should be added in:
76.60%
2.10%
19.10%
0%
2.10%
The Post-Neoadjuvant Situation
The Post-Neoadjuvant Situation
Particularly in Germany, neoadjuvant chemotherapy has established itself for most
patients with an indication for chemotherapy. Only recently, a meta-analysis confirmed
that neoadjuvant chemotherapy prior to surgery is as certain with regard to the oncological
outcome as adjuvant chemotherapy following surgery [74 ]. It is clear that patients after a lack of pCR have a significantly worse prognosis
than patients who achieved pCR [44 ], [46 ] or than the average of patients who received adjuvant chemotherapy [74 ]. Attempts have been made for some time to establish additional therapies for these
patients. In an Asian study, the disease-free survival and overall survival were able
to be improved for HER2-negative patients if post-neoadjuvant capecitabine was given
additionally after the surgery, after a lack of pCR following neoadjuvant chemotherapy
[75 ]. Similarly, it was shown in the case of HER2-positive patients that if no pCR could
be achieved following neoadjuvant anti-HER2 therapy with chemotherapy, therapy with
T-DM1 is more effective than standard treatment with trastuzumab [76 ]. Additional post-neoadjuvant studies have currently not yet ended, such as the PenelopeB
study [77 ]. The voting results regarding this interesting therapeutic situation can be found
in [Table 7 ] and demonstrate a high level of acceptance for post-neoadjuvant concepts.
Table 7 Votes regarding post-neoadjuvant therapy. There were 53 voting experts; the number
of those who did not vote is not known.)
Management of residual disease after neoadjuvant therapy: TNBC
If there is residual cancer in axillary LN or breast (≥ 1 cm residual cancer and/or
LN+) following neoadjuvant sequential AC → T chemotherapy for TNBC, your preferred
systemic therapy is:
6.20%
83.30%
2.10%
4.20%
4.20%
If there is residual cancer in breast only (< 1.0 cm residual cancer LN−) following
neoadjuvant sequential AC → T chemotherapy for TNBC, your preferred systemic therapy
is:
38.80%
51%
2%
2%
6.10%
Management of residual disease after neoadjuvant therapy: HER2+
If there is residual cancer in breast and/or axillary LN (no pCR/near pCR) following
neoadjuvant TCH or AC/EC → TH (without P), in HER2+ breast cancer, your preferred
systemic therapy is:
0%
0%
4.20%
91.70%
4.20%
If there is residual cancer in breast and/or axillary LN (≥ 1 cm residual cancer)
following neoadjuvant TCHP or AC/EC → THP, in HER2+ breast cancer, your preferred
systemic therapy is:
0%
0%
2%
93.90%
4.10%
Other Fields in the Treatment of the Early Breast Cancer Patient
Other Fields in the Treatment of the Early Breast Cancer Patient
Regardless of the optimisation of therapy, additional important fields in the treatment
of patients with early breast cancer have been discussed. These are no less important
than those discussed here in more detail. For a better overview, all voting results
are included in the appendix (supplementary Table S1 ). It shows results from the votes in areas such as pregnancy following breast cancer,
preservation of fertility, use of antiresorptive therapies (bisphosphonates, denosumab),
nutrition and physical activity as well as several aspects in the treatment of ductal
carcinoma in situ (DCIS). It is important that these aspects remain in the focus of
the patients and also the attending physicians. Overtreatment in the case of DCIS
is an area here which is as equally important as the concerns of patients who survive
breast cancer, such that life after the disease can be ensured with a quality of life
which is comparable to that of patients who never had breast cancer.
Outlook
While this yearʼs vote by the StGP showed that some of the questions from recent decades
are relatively clear today, a few other topics still led to controversial votes. All
of the voting results are available in supplementary Table S1 . However today, the format of the St. Gallen panel, in view of evidence-based guidelines
such as the S3 guideline and recommendations such as those of the AGO “Mamma” organ
committee, has a different meaning than at the time of its initiation 32 years ago.
While in the initial years, the votes in St. Gallen were like a guideline since there
was a lack of other guidance, they nowadays rather reflect an international atmosphere
which can provide help in clinical assessments and decisions, particularly in situations
in which there are no specific recommendations.
The next gains in knowledge are expected to be in relation to substances which have
already shown significant efficacy in the metastatic situation. Large, randomised
studies in the (neo)adjuvant therapy situation have been started for PARP inhibition,
CDK4/6 inhibitors and checkpoint inhibitors. Some of them have already completed recruitment
and thus corresponding results are expected in the near future.
