Breast cancer is the most common cancer in females (not including nonmelanoma skin cancers), with a lifetime risk of 1 in 8, or 12%. It is the second most common cause of cancer deaths in females (after lung cancer) and is most commonly sporadic (80% of cases). Approximately, 15% of cases are familial. Patients who are BRCA positive represent only a small proportion (5%) of all breast cancer patients. However, this patient group has a significantly increased risk of developing breast cancer (estimated at 70%). Male breast cancer is much less common and represents approximately 1% of all breast cancer cases with a lifetime risk of 1 in 1000.1,2
This patient has a number of risk factors for development of breast cancer. The most significant of these is her family history, having two first-degree relatives affected. Risk of developing breast cancer is generally stratified into three groups: strong, moderate, and low. Strong risk factors (RR >4) include age over 65, BRCA positive status, biopsy-confirmed atypical hyperplasia, and a personal history of breast cancer, none of which this patient has. Moderate risk factors (RR 2.1–4) include two first-degree relatives with breast cancer, high endogenous estrogen, high dose radiation to the chest, and high postmenopausal bone density, one of which this patient has. Low-risk factors (RR 1.1–2.0) include high alcohol consumption, early menarche (<age 12), late menopause (>age 55), nulliparity, late age at first pregnancy (>30), hormone replacement therapy (HRT), personal history of endometrial, ovarian, or colon cancer, obesity, and high socioeconomic status, a number of which this lady has.1,2
Patients seen in breast clinic with new-onset breast symptoms such as a mass, skin changes, or bloody discharge undergo formal assessment which begins with a complete medical history detailing specific information about the onset and duration of symptoms. It then progresses to include family and personal history of breast cancer and nonmalignant breast disease, information on menstrual status, pregnancies, lactation, hormone use, and previous breast surgery. In addition, all other aspects of a standard medical history such as long-term medical conditions, medications, allergies, and smoking status must be reviewed. This marks the beginning of the consultation but does not form part of the so-called “triple assessment” which starts with the physical examination and continues with imaging using mammography and ultrasound, and then pathologic assessment using image-guided core biopsy. Fine-needle aspiration cytology (FNAC) may be useful in some situations but is less preferable because it provides less information than a biopsy and in particular cannot distinguish between in situ and invasive disease. The triple assessment is, of course, undertaken as part of the multidisciplinary team meeting (MDT) process but the MDT per se is not one of the triple assessment parameters, nor is genetic screening which is only indicated in specific cases anyway. The aim of the triple assessment process is to be able to diagnose or exclude breast cancers in a “one-stop shop” setting so delay in diagnosis is minimized and patient attendances to clinic are also reduced.1–6
Breast screening has been shown to reduce mortality from breast cancer. However, the effectiveness of screening is dependent on the density of the breast, with lower sensitivity in higher density breast tissue. Screening mammography and diagnostic mammography differ in their protocols and views. Screening mammography consists of a mediolateral oblique view and a craniocaudal view of each breast. Diagnostic mammography involves additional views such as compression or magnification views used to further evaluate abnormalities found on screening or supplement clinical findings. Clinical examination, rather than imaging, must be performed with the patient supine and upright so as to avoid missing subtle changes in the skin and nipple not evident in only one position. In addition, the axillae must be examined. Ultrasound imaging is part of the standard assessment of the breast and can help to differentiate between solid and cystic lesions. It is also useful to guide biopsy sampling in clinic. MRI has a number of roles in breast imaging, not only recurrent tumor cases. For example, it may be useful in assessing tumor multifocality in patients wishing to pursue breast conservation treatment, and can be useful for assessing response to treatment with neoadjuvant chemotherapy and investigating occult primary tumors where patients present with axillary nodal metastases.1–3
Invasive ductal carcinoma is the most common histological subtype of malignant mammary tumors representing between 65 and 80% of all mammary carcinomas. Subtypes of ductal carcinoma include tubular, medullary, metaplastic, mucinous (colloid) papillary, and adenoid cystic carcinoma. Ductal carcinoma in situ (DCIS) represents an abnormal proliferation of malignant epithelial cells within the mammary ductal-lobular system without invasion into the surrounding stroma. Increased use of screening mammography during the past two decades has led to a marked increase in the number of patients with a diagnosis of DCIS and currently about 85% of all DCIS cases are detected solely based on mammography. The natural history of DCIS is only partially understood and its potential to progress to invasive breast cancer is uncertain. Paget’s disease of the nipple is a rare type of breast cancer involving the skin of the nipple. It starts in the breast ducts and spreads to the skin of the nipple and then to the areola. Paget’s disease can be associated with an underlying in situ or invasive component. Lobular carcinoma in situ (LCIS) is characterized by a solid proliferation of small cells with round to oval nuclei that distort the involved spaces in the terminal duct-lobular units. Although it is a marker for breast cancer risk, it is not a malignant finding. Invasive lobular carcinoma constitutes approximately 10–14% of invasive mammary carcinomas.1–3
6. Jan M, Mattoo JA, Salroo NA, Ahangar S. Triple assessment in the diagnosis of breast cancer in Kashmir. Indian J Surg 2010;72(2):97–103
7. A patient is discussed in the setting of the breast MDT with a 2.5-cm breast tumor, six positive axillary nodes, This patient has T2N2M0 disease and this is calculated based on the American Joint Committee on Cancer system1,2 as follows: Primary Tumor (T) • TX: Cannot be assessed • T0: No evidence of tumor • Tis: Carcinoma in situ • T1: Smaller than 2 cm • T2: 2–5 cm • T3: Larger than 5 cm • T4: Any size and invades chest wall or skin (includes inflammatory breast cancer) Lymph Nodes (N) • NX: Cannot be assessed • N0: No evidence of spread • N1: 1–3 axillary nodes • N2: 4–9 axillary nodes or enlarged internal mammary node • N3: 10 or more axillary plus mammary or supraclavicular nodes Metastasis (M) • MX: Cannot be assessed • M0: No distant disease • M1: Metastatic (most commonly bone, lung, brain, and liver)
Breast conservation therapy may be considered in patients with small primary tumors including nipple-areola complex (NAC), particularly in moderate to large breasts. Often the ratio of tumor to breast size is a major factor in the decision-making process and having large fatty breasts can lend itself well to wide local excision with a therapeutic mammoplasty, combined with a symmetrizing reduction performed on the opposite side. This approach relies on the principles of reduction mammoplasty, adapted to allow tumor resection with a more cosmetic approach. These are so-called “oncoplastic techniques.” The key contraindications to breast-conserving therapy are previous breast irradiation (as it cannot be given twice and will be required in breast-conserving treatment), recurrent or multifocal disease, tumors greater than 5 cm in diameter, inflammatory breast disease, and a high tumor size to breast size ratio. The need for clear margins is paramount in breast-conserving surgery as otherwise there is a two-fold risk of recurrence compared with negative margin results.1–4
This patient would have the pectoralis major muscle preserved. A simple mastectomy involves removal of the nipple-areola complex, breast parenchyma, and some of the breast skin (usually in a horizontal ellipse around the nipple), but the axilla is spared. A radical mastectomy as was originally described by Halsted, combined a simple mastectomy with axillary clearance and removal of pectoralis major. A modified radical mastectomy, as described in this case, involves a simple mastectomy and an axillary clearance with preservation of the chest wall musculature. Other, less-invasive mastectomy procedures include nipple-areola-sparing or skin-sparing techniques, which are regularly performed as prophylactic risk-reducing procedures in the absence of proven disease. These are also becoming more popular when breast disease is present and probably have similar overall survival and local recurrence rates to simple mastectomy for many patients.1,2
Sentinel lymph node biopsy (SNLB) has evolved out of efforts to minimize the morbidity associated with axillary lymph node clearance yet provide clinical information about the disease status of the axilla. It is a standard practice to combine blue dye and isotope as this better identifies the sentinel lymph node and when used in combination, the positive predictive value of the technique approaches 100%, with a negative predictive value close to 95%. Although sentinel lymph node metastases usually prompt axillary lymph node dissection, it is not always necessary because patients with a lower tumor burden (such as one to two positive nodes) undergoing whole breast irradiation will not need to have this performed. The disease status of the axilla is highly important in breast cancer as it represents one of the most significant prognostic factors. When formal axillary clearance is required, level II dissection is the extent of dissection preferred unlike in melanoma cases where all three levels are taken. Lymphedema is one of the key complications following axillary clearance but only a quarter of patients will normally develop lymphedema. Other potential complications include seroma, hematoma, infection, delayed wound heling, and potential nerve damage to the pectoral, long thoracic, and intercostobrachial nerves.1–7
as trastuzumab. Chemotherapy is commonly used for breast cancer patients and has been shown to improve overall survival. It may be used in the adjuvant or neoadjuvant setting. Decisions on its use include size of the primary tumor, lack of expression of estrogen or progesterone receptors, axillary involvement, HER2 status, and metastatic disease. One of the key indications for neoadjuvant chemotherapy is high-risk breast cancers, with the intention to downstage the primary breast and axillary nodal disease, thereby minimizing the extent of surgery. Furthermore, neoadjuvant chemotherapy allows for assessment of tumor response to treatment, which can be a vital information that would not otherwise be gleaned. Anthracycline-based regimens have become the basis for the adjuvant treatment of high-risk patients with breast cancer, often incorporating taxanes and targeted agents (anti-HER2 directed agents, e.g., trastuzumab and pertuzumab). Four major adjuvant trials, Herceptin Adjuvant (HERA), National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group (NCCTG) N9831, and Breast Cancer International Research Group (BCIRG) 006, have confirmed the effectiveness of trastuzumab in the adjuvant setting. These trials have shown that trastuzumab reduces the 3-year risk of recurrence by about 50% in this population.1–5 The addition of pertuzumab to trastuzumab and neoadjuvant chemotherapy has demonstrated increased frequency of complete pathological response rates.6 Tamoxifen has been shown to reduce the risk of relapse and mortality in randomized trials of women with estrogen receptor (ER)-positive (not negative) breast cancer. The standard treatment is for 5 years, but recent evidence from the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial showed that extending to 10 years reduced the recurrence and mortality for patients.7 A 10-year treatment plan is now currently recommended. Aromatase inhibitors such as Exesmestane are used to treat estrogen receptor–positive breast tumors in postmenopausal patients. Three double-blind, randomized, prospective studies—ATAC, the Intergroup Exesmestane Study (EIS), and the BIG 1-98 trial—have confirmed the superiority of aromatase inhibitors over tamoxifen in early stage cancers in postmenopausal women. All three studies have demonstrated an increase in disease-free survival.8,9,10 The American Society of Clinical Oncology now recommends aromatase inhibitors be used to lower the risk of recurrence in receptor-positive postmenopausal breast cancers as initial therapy or after treatment with tamoxifen.11
For most small to medium breast cancers, the survival rates are equivalent for breast conservation surgery or mastectomy.1 Breast conservation surgery is sometimes described as a lumpectomy or partial mastectomy and involves removal of the tumor with the surrounding portion of the breast. In almost all cases, postoperative radiotherapy is given. In contrast, patients who opt for a mastectomy do not usually require radiotherapy unless the tumor is particularly aggressive. Most patients have to weigh the risks and benefits involved with respect to either complete mastectomy or breast conservation surgery and radiotherapy. Her risk of local recurrence, overall survival, and disease-free survival is unlikely to be different whether the nipple is preserved or sacrificed, unless of course the nipple is involved with the disease. This evidence is based on a recent meta-analysis.2 There remains debate regarding immediate reconstruction, and two main issues need to be considered. First, should radiotherapy be required, will this treatment be compromised by the presence of a breast reconstruction in place. Second, will the reconstruction itself be compromised by the radiotherapy if required. Ideally, if radiotherapy is planned then reconstruction should wait until treatment is complete. If radiotherapy is unlikely to be required then immediate reconstruction is more safely indicated. As it stands there is evidence in both directions with some studies showing that radiotherapy did compromise delivery of radiotherapy,3,4 whereas other reports suggest that postoperative outcomes did not differ where reconstruction was or was not performed.5 In general, autologous reconstruction fairs better in response to radiotherapy than implant-based modalities. Overall decisions must be taken with the patients on an individual case-by-case basis to determine the best option for them bearing in mind the likely cancer treatment and the available reconstructive options for them.