Breast Cancer Landmark Atlas

What did the researchers want to learn?

In patients planned for breast-conserving surgery and radiotherapy who have one or two positive sentinel nodes, is it necessary to remove all the lymph nodes in the armpit?

What did this study change?

In suitable early-stage disease, routine completion axillary dissection has largely been abandoned; the aim is to reduce the risk of arm swelling while maintaining oncologic safety.

Benefit for patients

In selected patients, completion axillary dissection did not clearly improve overall survival or disease-free survival. As a result, in many patients the larger armpit operation can now be omitted.

Who does this apply to?

Depends on breast-conserving surgery plus whole-breast radiotherapy and on limited sentinel node involvement. It is not automatically extended to mastectomy, to more than three positive nodes, or to patients who do not receive radiotherapy.

What did the researchers want to learn?

In small breast cancer, is sentinel node biopsy always necessary if the armpit is clear on imaging and examination?

What did this study change?

Further reduction of axillary surgery in selected early-stage disease came onto the agenda.

Benefit for patients

In selected low-risk patients, omitting sentinel node biopsy may appear safe with regard to distant disease control. This does not mean the cancer will not be followed.

Who does this apply to?

Should not be generalized beyond the study's selection criteria. It is not the same clinical question as Z0011 / AMAROS.

What did the researchers want to learn?

In selected early-stage breast cancer, does doing no surgery at all on the armpit lymph nodes fall short of sentinel lymph node biopsy in terms of cancer recurrence?

What did this study change?

It showed that armpit surgery can be reduced further in suitable early-stage patients.

Benefit for patients

Five years later, the proportion of patients alive and free of invasive disease was 91.9% in the group without armpit surgery and 91.7% in the sentinel lymph node biopsy group; the non-inferiority criterion was met.

Who does this apply to?

Local recurrence in the armpit was numerically slightly higher in the group without surgery (1.0% and 0.3%). Patient selection is important; the results cannot be generalized beyond the study criteria.

What did the researchers want to learn?

In early-stage triple-negative breast cancer, does adding pembrolizumab to chemotherapy before and after surgery control the disease better?

What did this study change?

In suitable high-risk early triple-negative breast cancer, perioperative pembrolizumab plus chemotherapy became an important option.

Benefit for patients

In high-risk early triple-negative disease, adding pembrolizumab to chemotherapy increased the likelihood that the tumor disappeared completely at surgery and reduced events (recurrence or death). This does not mean immunotherapy for every triple-negative patient.

Who does this apply to?

For early-stage, high-risk triple-negative patients who meet the protocol criteria. The same result cannot be assumed for metastatic disease or low-risk early disease. The side-effect profile is assessed separately.

What did the researchers want to learn?

In early breast cancer, does removing the whole breast prolong survival compared with removing only the tumor and keeping the breast?

What did this study change?

In selected patients, breast-conserving surgery became established as an equivalent option to mastectomy; not everyone has to lose the breast.

Benefit for patients

In suitable early-stage patients, breast-conserving surgery plus whole-breast radiotherapy gave similar survival to removing the entire breast. The risk of local recurrence may differ somewhat, but this does not necessarily mean that survival is shorter.

Who does this apply to?

Applies only to patients with a suitable tumor size, safe surgical margins and a radiotherapy plan. It cannot be generalized to locally advanced disease or to situations in which radiotherapy cannot be given.

What did the researchers want to learn?

In patients with a positive sentinel lymph node, is armpit radiotherapy an acceptable alternative to complete removal of the armpit lymph nodes?

What did this study change?

It showed that in suitable patients, armpit radiotherapy is an alternative that can provide regional control with less arm swelling.

Benefit for patients

Within ten years, the rate of cancer coming back in the armpit was 0.93% with surgery and 1.82% with radiotherapy. No significant difference in survival was found. Five years later, the rate of arm swelling (lymphedema) was 24.5% with surgery and 11.9% with radiotherapy.

Who does this apply to?

Because recurrence events in the armpit are few, definite equivalence cannot be stated. Radiotherapy also has its own specific side effects.

What did the researchers want to learn?

In patients who are hormone receptor-positive, lymph node-negative and have intermediate genetic risk (21-gene recurrence score 11–25), does hormone therapy alone fall short of chemotherapy plus hormone therapy?

What did this study change?

It supported that chemotherapy can be omitted in many patients, especially those over 50 years of age with intermediate genetic risk.

Benefit for patients

Nine years later, the proportion of patients alive and free of invasive disease was 83.3% with hormone therapy and 84.3% with chemotherapy plus hormone therapy; overall survival rates were 93.9% and 93.8%.

Who does this apply to?

In some patients aged 50 or younger, especially when the score is 16–25, benefit from chemotherapy may be seen. The findings cannot be applied directly to lymph node-positive patients.

What did the researchers want to learn?

In patients who are hormone receptor-positive, have 1–3 positive lymph nodes and low-to-intermediate genetic risk, how does adding chemotherapy to hormone therapy affect the time before the disease comes back, according to menopausal status?

What did this study change?

It strengthened evaluating menopausal status and genetic risk together in the chemotherapy decision.

Benefit for patients

In postmenopausal patients, the proportion alive and free of invasive disease five years later was 91.9% with hormone therapy and 91.3% with chemotherapy added; there was no significant chemotherapy benefit. In premenopausal patients it was 89.0% and 93.9%; there was a significant difference in favor of chemotherapy.

Who does this apply to?

How much of the benefit seen in the premenopausal group comes from the direct effect of chemotherapy and how much from suppression of ovarian function cannot be fully separated.

What did the researchers want to learn?

In high-risk HER2-negative early breast cancer with an inherited BRCA1/2 alteration, does olaparib after surgery improve survival and the time before the disease comes back compared with placebo?

What did this study change?

It showed the importance of a PARP inhibitor after surgery in high-risk patients with an inherited BRCA alteration.

Benefit for patients

The updated six-year survival rate was 87.5% and 83.2% (hazard ratio for death 0.72). Invasive disease-free survival also improved (hazard ratio 0.65).

Who does this apply to?

It does not create a treatment indication for every BRCA alteration or every early breast cancer; the study's selection criteria must be taken into account.

What did the researchers want to learn?

In lymph node-positive, high-risk, hormone receptor-positive, HER2-negative early breast cancer, does adding abemaciclib to hormone therapy improve the time before the cancer comes back and survival?

What did this study change?

It supports the use of a CDK4/6 inhibitor after surgery in selected high-risk, lymph node-positive patients.

Benefit for patients

Seven years later, the proportion alive and free of invasive disease was 77.4% and 70.9%, and the survival rate was 86.8% and 85.0%. The survival benefit was statistically significant in the long-term analysis.

Who does this apply to?

It cannot be applied to all hormone receptor-positive patients. Side effects such as diarrhea, low white blood cell counts and clotting risk must be evaluated.

What did the researchers want to learn?

Does adding ribociclib to hormone therapy after surgery improve the time before the disease comes back? Is there a signal for long-term survival?

What did this study change?

It supports CDK4/6 inhibition after surgery in suitable stage II–III patients, including some high-risk lymph node-negative cases.

Benefit for patients

In the peer-reviewed five-year follow-up, the invasive disease-free survival hazard ratio was 0.716; the five-year absolute benefit was about 4.5 percentage points. A company announcement on 23 October 2026 reported a hazard ratio of 0.809 for six-year survival and an absolute benefit of 2.1 percentage points; this is not the peer-reviewed main publication.

Who does this apply to?

The six-year survival data are based on a company announcement and are separate from the peer-reviewed five-year result. Heart rhythm (QT prolongation), liver function and blood cell toxicity are important.

What did the researchers want to learn?

In patients in whom residual invasive HER2-positive disease is found at surgery after preoperative treatment, does T-DM1 improve the time before the cancer comes back and survival compared with trastuzumab?

What did this study change?

It is the key study supporting the use of T-DM1 after surgery in residual invasive HER2-positive disease after preoperative treatment.

Benefit for patients

Seven years later, the proportion alive and free of invasive disease was 80.8% and 67.1%; the survival rate was 89.1% and 84.4% (hazard ratio for death 0.66).

Who does this apply to?

It does not evaluate the same comparison for patients whose cancer disappeared completely at surgery. Severe (grade 3 or higher) side effects were more frequent with T-DM1.

What did the researchers want to learn?

Does old-style radical mastectomy improve 25-year survival compared with more limited operations (± radiotherapy or armpit approaches)?

What did this study change?

It is one of the historic studies that questioned the scientific basis for performing radical mastectomy routinely on every patient.

Benefit for patients

In the clinically lymph node-negative group, the 25-year survival rate was 25% with radical mastectomy, 19% with total mastectomy plus radiotherapy, and 26% with total mastectomy alone. No significant difference in survival was shown between the groups.

Who does this apply to?

It predates modern imaging, drug treatment and the sentinel lymph node era. It does not show that a more limited operation is sufficient for every patient.

What did the researchers want to learn?

Is breast-conserving surgery plus radiotherapy an acceptable alternative to removal of the whole breast in terms of 20-year survival?

What did this study change?

It supported the long-term cancer validity of breast-conserving surgery in suitable stage I–II patients.

Benefit for patients

The 20-year survival rate was 39.1% with breast-conserving surgery and 44.5% with mastectomy; the difference was not found to be significant. There was no significant difference in the time to development of distant metastasis.

Who does this apply to?

Older surgical and radiotherapy techniques were used. Recurrence in the same area and survival must be evaluated separately.

What did the researchers want to learn?

In patients with small involvement of up to 2 mm in the sentinel lymph node, does not removing the armpit lymph nodes fall short of removing them in terms of the time before the disease comes back?

What did this study change?

It supported omitting armpit clearance in suitable patients with small sentinel lymph node involvement of up to 2 mm.

Benefit for patients

Ten years later, the proportion of patients alive and disease-free was 76.8% in the group without lymph node clearance and 74.9% in the group with it (hazard ratio 0.85); the non-inferiority criterion was met. Arm swelling was 4% and 13%.

Who does this apply to?

It cannot be generalized to patients with larger involvement or clinically evident armpit disease.

What did the researchers want to learn?

In selected hormone receptor-positive early breast cancer in patients aged 70 and over, does omitting radiotherapy harm survival; what is the difference in recurrence in the same area?

What did this study change?

In low-risk, elderly patients for whom hormone therapy is planned, omitting radiotherapy can be considered through shared decision-making.

Benefit for patients

Ten years later, the rate without recurrence in the same area was 98% in those who received radiotherapy and 90% in those who did not. Survival rates were 67% and 66%, with no significant difference.

Who does this apply to?

Omitting radiotherapy increases the risk of recurrence in the same area. Adherence to hormone therapy and patient preferences are important.

What did the researchers want to learn?

In patients aged 65 and over who are hormone receptor-positive, lymph node-negative and have small tumors, does omitting radiotherapy increase ten-year local recurrence; is survival affected?

What did this study change?

It showed that radiotherapy can be omitted in selected patients, but that this carries a significant cost in terms of local control.

Benefit for patients

Ten years later, the rate of recurrence in the same area was 9.5% in those without radiotherapy and 0.9% in those who received it. The survival rate was 80.8% and 80.7%.

Who does this apply to?

Omitting radiotherapy does not provide the same local control. Patient selection and adherence to hormone therapy are decisive.

What did the researchers want to learn?

In patients who are clinically high-risk but genetically low-risk, does omitting chemotherapy keep survival without distant spread at an acceptable level?

What did this study change?

It supported evaluating clinical risk and genetic risk together and reducing chemotherapy in selected patients.

Benefit for patients

In the main test group that did not receive chemotherapy, the proportion of patients alive without distant spread at five years was 95.1%. In the randomized group, at eight years this rate was 92.0% with chemotherapy and 89.4% without. In hormone receptor-positive patients aged 50 or younger, a difference of about 5 points in favor of chemotherapy was seen, but this finding is exploratory.

Who does this apply to?

Low genetic risk does not mean that no benefit from chemotherapy will definitely be seen; careful evaluation is needed, especially in younger patients.

What did the researchers want to learn?

In patients with macrometastasis (large involvement) in the sentinel lymph node (1–2 nodes), does sentinel biopsy alone fall short of removal of all the armpit lymph nodes?

What did this study change?

It broadened the evidence supporting reduced armpit clearance in suitable patients.

Benefit for patients

Five years later, the proportion of patients alive without the cancer coming back was 89.7% in the sentinel-biopsy-only group and 88.7% in the armpit clearance group (hazard ratio 0.89); the non-inferiority criterion was met. The results should be interpreted in settings in which radiotherapy to the lymph node region was frequently given.

Who does this apply to?

The results should be interpreted in the study conditions in which radiotherapy to the lymph node region was commonly given. It does not show that all armpit treatments can be omitted in every patient.

What did the researchers want to learn?

In patients with 1–2 positive sentinel lymph nodes, is additional armpit surgery or radiotherapy necessary?

What did this study change?

When the results are available it may be important for further reduction of armpit treatment; for now it cannot be said to have changed standard treatment.

Benefit for patients

Because mature main results have not been confirmed, survival, armpit recurrence and non-inferiority rates are not given on the card. The results publication and registration status need to be re-verified.

Who does this apply to?

It is not entirely the same clinical question as the one answered by the SENOMAC and Z0011 studies. Clinical practice should not be changed until the results have been announced and verified.