The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch multicentre cohort study l

Breast cancer is the most common cancer in women worldwide with rising survival
rates thanks to more extensive (adjuvant) treatment regimen. Consequently, more
attention is warranted for the lifetime morbidity of breast cancer survivors
resulting from the current treatment regimes. The ACOSOG Z0011 study
demonstrated no additional value of a completion axillary lymph node dissection
in sentinel lymph node positive breast cancer patients undergoing breast
conserving surgery and adjuvant radiation and systemic treatment. This
emphasizes what was already suggested many years ago by the NSABP B-04;
completion axillary treatment does not contribute to survival nor disease
control and can therefore be considered as overtreatment. As a result of the
axillary lymph node dissection, many patients suffer from short and long term
morbidity, such as seroma (15-75%), lymph edema (20%), nerve injury (55-75%)
and reduced shoulder function (16%). Study results of the ACOSOG Z0011 could
not be implemented in all sentinel lymph node positive patients, because the
study only concerned patients undergoing breast conserving therapy. It has
been suggested that the results of the ACOSOG Z0011 study might be ascribed to
accidental irradiation of part of the axilla by the tangential breast
irradiation. Therefore, this study investigates whether completion axillary
treatment can also be safely omitted in sentinel lymph node positive breast
cancer patients undergoing a mastectomy.

The study aim is to decrease the number of breast cancer patients receiving
overtreatment of the axilla, in order to positively influence the axillary
morbidity rate and quality of life. Therefore, we investigate whether
completion axillary treatment can be safely omitted in sentinel lymph node
positive breast cancer patients treated by mastectomy, in terms of non-inferior
regional control, distant-disease free and overall survival. All objectives are
measured during a follow-up of 10 years.

A non-inferiority multicenter cohort study. Patients who meet the in- and
exclusioncriteria will be treated (shared decision making) after informed
consent for one of the two treatment methods:
- Arm A (control arm): mastectomy with completion axillary treatment according
to the Dutch breast cancer guideline.
- Arm B (experimental arm): mastectomy without further axillary treatment
Stratification: Age (*50, 50*75, >75 yr), oestrogen receptor status (positive
vs. negative), HER2neu status (amplified vs. not amplified), sentinel lymph
node metastasis (micro-/macrometastasis), clinical tumor size (<3cm/*3cm),
grading according to modified Bloom-Richardson (I-II/III), primary systemic
therapy and participating center.
Adjuvant radiation or systemic treatment is administered according to the Dutch
guideline. Primary systemic therapy in cT1-2 patients (initial stage) is no
exclusion criterion in case the sentinel lymph node procedure is performed
before the start of the therapy.
Yearly follow-up with physical examination of the axilla for 10 years. Axillary
ultrasound (+/- tissue sampling) on indication. Staging for distant metastases
and/or a delayed axillary lymph node dissection if indicated by the
multidisciplinary team.
Validated questionnaires are used to assess axillary morbidity rate and quality
of life (Lymph-ICF, QLQ-C30, QLQ-BR23) and to measure if anxiety and
personality traits influence the outcome of quality of life (STAI-trait,
NEO-FFI) in 700 of 878 patients. These questionnaires are provided at the day
of inclusion and sequentially post inclusion at 6 months, 1, 2, 5 and 10 years.

Patients in the experimental arm will not receive completion axillary
treatment. Patients in the control arm will undergo completion axillary
treatment according to the Dutch breast cancer guideline.

There is no extra burden for participating patients as regard to additional
diagnostic tests/interventions and follow-up. Any additional burden for the
patient will only consist of completing quality of life questionnaires in 700
of 878 study patients. These questionnaires are provided at the day of
inclusion and sequentially post inclusion at 6 months, 1, 2, 5 and 10 years.

We hypothesize that omitting the completion axillary treatment is not inferior
to the standard treatment. Nevertheless, possible disadvantages are a worse
regional recurrence rate, and delayed axillary treatment if indicated.
Patients in the experimental arm have the possible advantages of less
morbidity, fewer operations and hospitalizations and an improved quality of
life, compared to patients treated with completion axillary treatment.

No patient will encounter any delay in their treatment as a result of
inclusion.