11
• Image-guided biopsy, either FNA cytology or histo- logical core biopsy; image-guided biopsy is preferred even in palpable lesions.
Ideally this process should be executed within 2 weeks after referral and diagnosis discussed with the patient within 1 week 12 . Before disclosing diagnosis and discussing ther-
apeutic consequences with the patient, all imaging and histological/cytological results and further management of the patient with alternatives, are discussed in a multi- disciplinary meeting.
If the diagnosis is unequivocally benign, the patient can be referred back to screening or the general practitio- ner with a minimal risk of misdiagnosis of malignancy 19 .
When a histological core biopsy shows atypical features, frequently referred to as atypical ductal hyperplasia, lobu- lar carcinoma in situ (lobular neoplasia), or sclerosing adenosis, the chance of associated malignancy is more than 5%. In such situations, an image-guided open surgi- cal biopsy (see below) is advised 20 .
If cancer is diagnosed, either in situ or invasive, further treatment strategy steps should be taken. In invasive cancer, further assessment of size and lymph node involvement is warranted. Particularly in younger women ( < 55–60 years) in whom breast conserving therapy is considered, MRI of the breast is of help to better esti mate size, multifocality and contralateral breast cancers 21 , 22 . Also,
if upfront neoadjuvant systemic therapy by chemotherapy or hormonal therapy is considered – although rare in screen- detected cancers – MRI is of more help for further monitor- ing of this therapy as compared with clinical examination, mammography, or ultrasound 23 – 25 . Furthermore, ultra-
sound of the axilla to screen for lymph node metastasis is very useful: to prevent one sentinel node procedure, approximately six ultrasounds of the axilla have to be performed 26 , 27 . Nowadays, most breast radiologists will
screen the axilla for lymph node metastasis if a malignancy in the breast is suspected at the same time. If a suspicious lymph node is encountered, ultrasound directed FNA cytology or core biopsy should be taken. All this will lead to an optimal surgical treatment strategy to be discussed with the patient. It is aimed for that more than 90% of patients with breast cancer have their diagnosis before any surgical intervention 12 , 13 , 28 , since it is generally accepted
that the chance of successful first – therapeutic – surgical intervention is highest with optimal imaging and known diagnosis of breast cancer 28 . The diagnostic strategy of
screen-detected breast lesions is summarized in Algorithm 1 .
SURGERY
The aim of the resection of an in situ or invasive breast cancer is to achieve clear margins and a good
cosmetic outcome 13 , 28 . Screen-detected breast cancers are
usually non-palpable. This has two implications for surgery: (1) Most patients can or preferably should be treated with
breast conserving therapy, since a majority of lesions are small;
(2) The surgeon should be guided to the lesion to facilitate complete excision.
A number of guiding tools are available in non-palpable cancers: the guide wire 29 , multiple bracketing guide
wires 30 , charcoal or other dyes 31 – 33 , and radioactive tracers,
for instance technetium-99m colloid 34 , 35 , iodine-125 seeds 36 .
The advantage of the guide wire is the general availability, relatively easy application and low costs 37 . The disadvan-
tages are that frequently the wire is inserted not via the shortest route and not near the lesion leading to incom- plete excision or even missed excisions 38 . The advantages
of radioactive occult lesion localization (ROLL) are two- fold in that exact localization is possible with a drop of the radioactive tracer in the center of the lesion, either by ultrasound or stereotaxis, and the possibility of perform- ing lymphoscintigraphy and probe-guided sentinel node identification 39 , 40 . Radioguided excision biopsy appears to
lead to more complete excisions as compared with guide wire excisions 41 , 42 . In palpable cancer a wide local excision
on palpation is performed.
A wide local excision, aiming to resect with a 1-cm free margin, is best performed by a so-called segmental exci- sion 43 . In principle a full thickness excision of breast
parenchyma from skin (may be included) to fascia, and subsequently the lateral borders of the cancer and ending with the central (nipple) side of the parenchyma should be performed. The specimen should be marked for the pathologist to facilitate eventual re-excisions. Preferably the resection should be performed in one specimen and if more excisions are performed, careful re-orientation to secure margin assessment is mandatory 44 . After excision,
the breast tissue should be adapted by mobilization of parenchyma flaps or by other oncoplastic techniques 45 , to
minimize dead space and to provide the best possible cos- metic result. The advantages of closing breast tissue and minimizing that space are less seroma/hematoma forma- tion, fewer complications, usually a good cosmetic result, and less fibrosis in the long term 43 – 46 .
If the breast cancer is too large (DCIS, or infiltrating cancer with or without extensive intraductal component) to achieve clear margins or a good cosmetic outcome, large excision with latissimus dorsi muscle-mini-flap or skin- sparing mastectomy with reconstruction (implant or free flaps) are the methods of choice. Of course patients should be informed about possibilities of breast reconstruction and this should be performed according to the wishes of the patient 47 . If well informed, many women do prefer to have
a breast reconstruction immediately resulting in fewer operative procedures and a better cosmetic outcome 48 , 49 .
If lymph nodes in the axilla are proven to be involved, a complete axillary lymph node dissection should be per- formed in the same session 28 .
DCIS is a proliferation of morphologically malignant cells within the ducts and lobules of the breast without evidence, by light microscopy, of invasion through the basement membrane into the surrounding stroma. The optimal treatment of DCIS is controversial. In the pre- screening era DCIS was rare and accounted for 2–3% of all breast cancers. At that time, mastectomy was the treat- ment of choice. Nowadays the proportion of DCIS among screen-detected breast cancers has increased
to 20% 50 . It is not known whether all these DCIS will
progress into symptomatic and/or invasive lesions 51 . Since
breast-conserving treatment (BCT) became an appropri- ate alternative for mastectomy in women diagnosed with invasive breast cancer 52 , this treatment modality as a
matter of course was also tested in DCIS. In several ran- domized clinical trials wide local excision (WLE) alone was compared with WLE and radiotherapy, and it was shown that by adding radiotherapy a 40–50% reduction of local failure could be achieved compared with WLE alone with a local recurrence rate of 15% at 10–12 years 53 , 54 .
As a result of this obvious beneficial local effect of radio- therapy, the breast cancer-specific death rate is the same for all treatments 53 – 55 .
Referral
MDM
MDM MDM BIRAD III–V
Add: Image-directed biopsy
(Fine needle aspiration / core biopsy)
Benign BIRAD I–II
Benign* Benign risk lesion†
Image-direced surgical biopsy
Malignant‡
Treatment Back to screening
Malignant‡
Benign*
Assessment by breast radiologist: Breast ultrasound
•
Mammography ± magnification view •
Algorithm 1 Screen-detected breast lesions. * Benign: no signs of malignancy in sufficient number of representative core biopsies,
concordant with mammographical lesion, and agreed in multidisciplinary meeting (MDM). † Benign risk lesion with > 5% chance of
associated cancer: atypical ductal hyperplasia, sclerosing adenosis. ‡ Malignant: ductal carcinoma in situ any invasive cancer. BIRAD, Breast
STAGING
About 90% of screen-detected breast cancers are stage 1 or 2 ( < 5 cm, clinically node negative). In these patients distant metastasis are rarely found at primary diagnosis ( < 1%) 56 . In general, no routine assessment or search for
distant disease with imaging techniques or biochemical tests is warranted in women with screen-detected breast cancer. Lymph node involvement is found in up to 20% of patients with a small (usually screen-detected) breast cancer 57 . Once invasive cancer is diagnosed on core
biopsy, a sentinel node procedure can be considered as standard care 58 . If not available, an axillary lymph node
dissection can be performed as well. In ‘pure’ DCIS diag- nosed on an excision specimen (either wide local excision or ablative) and after full histological work-up, lymph node involvement is extremely rare and lymph node stag- ing is not necessary 59 . Nowadays most DCIS is diagnosed
after stereotactic or ultrasound-guided core biopsies. The nature of the disease is underestimated in 13–38% of patients diagnosed with core needle biopsy to have DCIS 60 , 61 . Therefore, about a quarter of patients diag-
nosed with DCIS on core biopsy will have invasive cancer. Most probably this occurs as result of a sampling error since only a small part of the lesion can be examined by this minimal invasive technique, which is used for preoperative diagnosis in about 80% of the patients 62 .
Consequently, these patients are at risk of having axillary metastases. Lymphatic mapping by sentinel lymph node biopsy (SLNB) is an accurate technique with a low mor- bidity to investigate nodal involvement in invasive breast cancer and is also considered in the initial management of patients diagnosed with DCIS. At present, there are no uniform criteria to select patients who benefit most from SLNB. When invasive cancer is found after definitive surgery, lymph node staging should have been indicated. This finding has led to the reasonable practice that the sentinel node procedure is performed in patients with extensive DCIS for whom ablative surgery is indicated. Particularly when breast reconstructions are performed, axillary lymph node dissection later is difficult. Also, in patients with DCIS and possible signs of invasion on mammography, ultrasound, or MRI and scheduled for breast conserving therapy, a sentinel node procedure can be performed 63 – 66 .