Breast Diseases: Carcinoma of the Breast PDF

# Breast Diseases ## Carcinoma of the breast **Introduction:** - The breast is the most common site of cancer in women. - In the USA, one in every nine women is expected to develop cancer in their lifetime. - In Egypt, breast cancer occurs at a younger age than in western countries and it accounts...

# Breast Diseases ## Carcinoma of the breast **Introduction:** - The breast is the most common site of cancer in women. - In the USA, one in every nine women is expected to develop cancer in their lifetime. - In Egypt, breast cancer occurs at a younger age than in western countries and it accounts for about 35% of total malignancies among Egyptian females, representing the commonest malignant neoplasm in females. **Incidence:** - **Race**: Black and Asian women are less affected. - **Age**: In high-risk populations, the risk generally increases progressively with age. In low-risk populations, the risk increases and reaches a plateau at the age of 50. **Etiology**: The exact etiology of breast cancer is not known. Genetic, endocrinal or environmental factors may have a role. ### **[A] Genetic Factors:** - It has been proven that, in 5-10% of all cases of breast cancer, there is an autosomal inheritance of a mutant gene. Two genes BRCAI (on chromosome 17) & BRCAII (on chromosome 13) are incriminated. These cancers usually occur at a younger age and are multifocal & bilateral. - Presence of breast cancer in the mother or sister increases the risk by 2-3 times while presence of the disease in both the mother and sister increases the risk by 14 times. ### **[B] Endocrinal Factors:** 1. Cancer in the other breast 2. Atypical epithelial hyperplasia 3. Menstrual history: Early menarche (under 12 years), late menopause (after 50 years) 4. Obesity and high intake of saturated fatty acids: Steroid hormones are converted to estradiol in fatty tissues 5. Pregnancy: Late first pregnancy (after age of 30), nullipara 6. The relation to oral contraception is not exactly known. ### **[C] Precancerous Lesions:** 1. Moderate or marked epithelial hyperplasia & duct Papilloma: Increase the risk by 1.5-2 times. 2. Atypical epithelial hyperplasia: Increases the risk by 2-5 times. 3. Lobular or ductal carcinoma in situ: Increases the risk by 5-10 times. **Site:** - Inner, lower (6%): Is the rarest & worst --> spread to subdiaphragmatic lymphatics. - Upper, outer (60%): The commonest --> largest volume of breast tissue. - Central part (12%): The 2nd common --> spread to subareolar area from neighboring tissue. - Lower, outer (12%). - Upper, inner (10%). **Pathology:** There are the following pathological types: ### **[A] Carcinoma of the Ducts:** 1. **Non-infiltrating (ductal carcinoma in situ): 6%** - *(a) Comedocarcinoma* - *(b) Non-comedocarcinoma (Papillary or solid)* 2. **Infiltrating ductal carcinoma:** - *(a) Schirrhous carcinoma 70-75%* - *(b) Encephaloid carcinoma 10%* - *(c) Mucinous carcinoma 3%* ### **[B] Carcinoma of the Lobules:** 1. **Non-infiltrating lobular carcinoma (in situ) 0.7%.** 2. **Infiltrating lobular carcinoma 7.5%.** ### **[C] Paget's disease of the nipple (1%):** 1. **Nature:** An Intraduct carcinoma which begins in the epithelium of a main duct and spreads to the skin of the nipple and down into the breast substance. 2. **When the nipple epithelium is infiltrated, it produces nipple erosion. **In early stages a mass may not be palpable, a mass may only appear after 2 years from the start of the disease. 3. **Histologically:** there are: - *(a) Paget's cells:* Clear vacuolated cells, with small dark staining nuclei, which occur alone or in clusters in the deep layers of the epidermis. - *(b) Hyperplasia of all layers of the epidermis.* - *(c) Round cell infiltration of the dermis.* N.B:James Paget (1809-1892) is a pathologist-university of cambridge. ## Hormone Receptors: - About 60% of breast cancers have receptors for estrogen & are termed ER-positive. - These tumors are hormone dependent & respond more to hormonal treatment. - Tumors may also have progesterone receptors. - Recently: tumors are stained for c-erb 52 (growth factor receptor). If proved to be positive, monoclonal antibodies against these receptors could be used. NB: li-fraumini syndrome: Mutation in tumor suppressor gene p53 leading to: Malignancies in breast, ovary, colon and lymphomas ## Spread: - Previously it was thought that breast cancer spreads locally at first, then by lymphatics and lastly by the blood stream. - This view is no longer accepted and it is now well realized that carcinoma of the breast may spread by the blood stream very early producing micro-metastases in distant organs. ### **[A] Local Spread:** - Can occur through the breast substance, overlying skin- underlying pectoralis major and serratus anterior muscles and the chest wall. ### **[B] Lymphatic Spread:** - By embolism and permeation is mostly to the axillary nodes, next common is the internal mammary chain. - Involvement of the supraclavicular node is considered an advanced disease. 1. **Axillary lymph nodes are classified into 3 levels:** - Level I: Below the pectoralis minor muscle. - Level II: Behind the pectoralis minor muscle. - Level III: Above the pectoralis minor muscle. 2. **Mammary lymph nodes lying along the internal mammary vessels** in the first three intercostal spaces. They receive part of the lymph from the medial half of the breast. 3. A few lymphatics pierce the pectoralis major muscle to drain into the inter-pectoral L.N. (lymph nodes of Rotter) and pass to the posterior intercostal lymph nodes. 4. **Lymphatics from the lower inner quadrant:** may pierce the rectus sheath to reach the peritoneal lymphatic plexus. 5. **Supraclavicular lymph nodes:** may be affected by retrograde lymphatic spread. 6. **Obstruction of the dermal lymphatics by malignant cells produces breast skin edema** that is marked in the dependant part, i.e. the lower half of the breast. The edematous skin is pulled at the sites of hair follicles, sebaceous glands and sweat glands giving the appearance of an orange peel, hence the French name Peau d' Orange. ### **[C] Blood stream spread:** - Produces metastasis in the lungs, bones, brain and liver. N.B: part of the venous drainage of the breast goes to intercostal veins which drain into the azygos system and communicates with valveless vertebral venous plexus. This explains the tendency of breast cancer deposits to affect the axial skeleton ## Staging: ### **[A] International TNM staging:** * **T = Tumor** - Tis: Carcinoma in situ. Paget's disease with no palpable tumor. - TO: No evidence of primary tumor. - T1: 2 cm diameter or less. - T2: 2-5 cm diameter. - T3: Tumor larger than 5 cm. - T4: Any size with direct extension to chest wall or to skin. * **N = Nodes** - NO: No palpable axillary nodes. - N1: Mobile palpable homolateral axillary nodes. - N2: Fixed homolateral axillary nodes. - N3: Palpable homolateral supraclavicular nodes. Edema of the arm. * **M = Metastases** - MO: No evidence of distant metastases. - M1: Distant metastases. ### **[B] Staging of the UICC (union international center cancer) is now internationally approved.** It is based on the TNM staging: | Stage UICC | description | category | 5 year survival (%) | |---|---|---|---| | I | T1,NO,MO | Early breast cancer | 93 | | II | IIA | T2,N1,MO | Early breast cancer | 72 | | | IIB | T3,NO,MO | | | | III | IIIA | T1-3,N0-2,MO | Locally advanced | 41 | | | IIIB | T4,any N,MO | Breast cancer | | | IV | | Any T,any N,M1 | metastatic | 18 | ### **[C] Manchester classification:** * Stage I: - A mobile mass in the breast. * Stage II: - A mobile mass in the breast with or without skin tethering. - Palpable mobile homolateral axillary nodes. * Stage III: - Peau d' orange larger than the tumor but still limited to the breast. - Tumor fixed to the pectoral muscle but not to the chest wall. - Homolateral axillary lymph nodes matted together or fixed to chest wall. - Homolateral supraclavicular lymph nodes. - Edema of the arm. * Stage IV: - Skin involvement wide of the breast (cancer en cuirasse). - Fixation to the chest wall. - Distant metastases. - involvement of the opposite breast or axilla. ## Clinical Features: ### **I- Symptoms:** 1. The patient accidentally notices a painless lump in the breast. An accidental trauma to the breast may attract the attention of the patient to presence of the lump. 2. Much less frequently the disease is discovered because of mild breast pricking pain, nipple retraction or blood stained nipple discharge. 3. Picture of metastasis (lymph node or blood). 4. The disease may be discovered by routine screening mammography. ### **II- Signs:** Some of the following signs may be detected: ### **[A] Breast:** 1. Asymmetry. 2. Enlargement. 3. Skin dimpling. 4. Skin puckering. 5. Peau d'orange (orange peel). 6. Skin nodules. 7. Skin ulceration. * Dimpling and puckering of the skin are evident when the patient is sitting and elevates her arms. * Peau d'orange, skin nodules, and ulceration indicate a locally advanced disease. ### **[B] Mass:** 1. Hard. 2. Irregular. 3. Ill-defined. 4. Restricted mobility within the breast substance. 5. Fixation to the skin, underlying muscles, or chest wall, if present, is diagnostic of carcinoma. ### **[C] Nipple:** 1. Recent retraction. 2. Change of direction. ### **[D] Axillary and supraclavicular nodes:** - Number and mobility of palpable nodes are assessed. ### **[E] Distant metastases:** 1. Chest examination. 2. Hepatomegaly. 3. Ascites. 4. Pelvic examination for hard deposits or Krukenberg tumor. ## Skin Manifestations of Breast Cancer 1. **Dimpling and puckering of the skin:** Overlying the tumor. This is the earliest manifestation of superficial tumors. It is due to infiltration of Cooper's ligaments by the tumor, pulling the skin toward the tumor. (Cooper's ligament: Are conical fibrous tissue normally connecting the skin to the pectoral fascia). 2. **Fixation.** 3. **Fungation.** 4. **Ulceration:** Ulcer is always indurated. 5. **Skin nodules:** Near or far from the tumor, even around the umbilicus. They are due to lymphatic spread. 6. **Peau d' orange:** non-pitting edema due to obliteration of the skin lymphatics by malignant permeation & surrounding fibrosis. The pits giving skin the orange appearance are due to hair follicles, sweat glands & sebaceous glands anchored to the skin. 7. **Cancer en cuirasse:** In very late cases, due to malignant infiltration and fibrosis of the skin as well as lymphatic obstruction, the skin is very hard, very thick, and non-mobile like a shield. 8. **Nipple:** Is retracted. 9. **Paget's disease of the nipple.** ## III- Special Clinical Forms: ### **1. Paget's disease of the nipple: (1% of breast cancers)** - The first symptom is often an abnormal pricking sensation of the nipple, with superficial erosion. - A tumor mass may not be palpable. - The lesion is commonly mistaken for eczema. - The diagnosis is established by biopsy of the erosion. | | Paget's disease | Eczema | |---|---|---| | 1 | Unilateral | Commonly bilateral | | 2 | Usually occurs at menopause | Commonly occurs at lactation | | 3 | No itching | Itching | | 4 | No vesicles-not oozing (dry) | Vesicles-oozing | | 5 | Nipple is eroded | Intact nipple | | 6 | Well-defined margin | Ill defined margin | | 7 | A breast lump may be felt | No lump | | 8 | No response to eczema treatment | Responds to treatment | | 9 | Starts in the nipple | Starts in the areola | ### **2. Inflammatory Carcinoma:** - This is a rare aggressive form of breast cancer. - Usually occurs during pregnancy or lactation. - There is a rapidly growing, sometimes painful, breast swelling. - The overlying skin becomes red, edematous and warm. Often there is no distinct mass, since the tumor Infiltrates the breast diffusely. - The picture clinically resembles acute mastitis. - **Prognosis:** Is poor as it is usually advanced at the time of diagnosis. | | Inflammatory carcinoma | Acute bacterial mastitis | |---|---|---| | | Gradual onset with no or low grade fever | Acute onset with high fever | | | Progress is slower | Rapid progress | | | Involves more than one third of the breast | One breast sector is affected | | | Skin is dusky red | Skin is rosy or bright red | | | Mildly tender or non-tender lesion | Markedly tender lesion | | | Non-tender axillary nodes | Tender axillary nodes | | | No response to antibiotics in one week is an indication for biopsy | The lesion is either cured by antibiotics or forms an abscess | ### **3. Carcinoma In situ:** | carcinoma in situ | Duct carcinoma in situ (DCIS) | Lobular carcinoma in situ (LCIS) | |---|---|---| | Frequency | More common | Less common | | Bilaterality and Multicentricity | Rare | common | | Microcalcifications | Present | absent | | Early detection | Possible | Less likely | | Potential for invasive cancer | 30-50% | It is a marker of increased risk of malignancy in the same or other breast | | Treatment | As invasive cancer | Strict follow up. | ## Differential Diagnosis: ### **I- Case presenting by a lump (mass):** | Items | 1. Carcinoma | 2. Solitary cyst | 3. Fibrocystic disease | 4. Fibroadenoma | |---|---|---|---|---| | Age | Usually > 35 yrs | 35-55 years | 20-55 years | 15-30 years | | Pain | Painless | Occasionally painful | Occasionally painful | Painless | | Surface | Irregular | Smooth surface | Indistinct surface | Smooth may be lobulated | | Consistency | Stony hard | Fluctuation is difficult to elicit, so It feels soft to hard | Firm, ill defined areas of thickening | Firm, highly mobile | | Lymph nodes | Probably axillary node enlargement | Free axilla | Free axilla | Free axilla | The above lesions constitute 95% of breast lumps. **Other less common causes are:** 1. Traumatic lesions: hematoma and fat necrosis. ### **Breast hematoma:** - If there is no external bruising, a deeply seated old hematoma may form a hard mass that greatly resembles a carcinoma. ### **Traumatic fat necrosis:** - Blunt breast trauma may cause death of some of the fat cells. - The liberated fatty acids combine with calcium to form calcium soaps. - The result is one of two forms: 1. A cyst that contains thick oily fluid is formed. 2. Less frequently a hard mass, which resembles a carcinoma, is formed. ### **6. Inflammatory lesions:** Chronic abscess, mammary duct ectasia & T.Β. | | Chronic breast abscess | Τ.Β. | Mammary duct ectasia | |---|---|---|---| | | This is the result of Improper treatment of acute abscess. There may be (with the mass) nipple retraction and skin puckering. However it is more painful than carcinoma and is accompanied by low-grade pyrexia. | Presents as: 1. Multiple cold abscesses & sinuses. OR 2. Multiple nodules in the breast substance. | The affected area is hard & may be associated with skin dimpling & nipple retraction simulating carcinoma. It is called plasma cell mastitis due to predominance of plasma cells. | ### **7. Other cysts:** e.g. Galactocele. ### **8. Other tumors:** Duct papilloma accumulating blood behind it and sarcoma (very rare). ### **9. Swellings arising from the chest wall:** Tuberculosis or tumor of a rib or lipoma. ## II- Paget's disease: Should be differentiated from eczema of the nipple. ## III- Inflammatory carcinoma: Should be differentiated from an acute breast abscess. ## IV- Nipple retraction: Two types of nipple retraction should be identified: - **Longstanding type** dates back to the puberty is an innocent finding. It poses difficulty only during lactation. It predisposes to mastitis and resolves spontaneously after lactation. - **Recent nipple retraction in womanhood** is considered seriously. One cause is carcinoma. Other causes are mammary duct ectasia, TB and chronic breast abscesses. ## Investigations: ### **[A] Laboratory:** CEA and Cancer antigen CA 15-3.It is prognostic rather than diagnostic. ### **[B] Mammography:** - Is soft tissue radiology of the breast. In expert hands it is 95% accurate in diagnosing breast cancer. - It is useful in detecting multifocal lesions in the same or other side. - A cancer appears as a dense opacity containing microcalcifications and has an indefinite outline. N.B1: only 20% of microcalcifications are malignant. N.B2: xero-radiography: as mammography but more accurate. ### **[C] Ultrasonography:** - A speculated hypo-echoic mass more deep than wide suggests a malignant lesion. - It differentiates between chronic abscess & carcinoma. - It differentiates between solid & cystic lesions. - Malignant lesion receives blood flow from all around with turbulent speed. - It is particularly useful in young women in whom mammography is not helpful. ### **[D] Magnetic resonance imaging (MRI):** it is indicated with contrast in certain situations e.g. - Postoperative scarring to differentiate between fibrosis and local recurrence of malignancy. - After neoadjuvant therapy to monitor response. - In the presence of breast implants ### **E) Biopsy:** 1. **Excision biopsy:** Is the most reliable and provides a big specimen to allow for hormone receptor estimation as well. 2. **Frozen section biopsy:** The biopsy is frozen and slides are prepared from the frozen block. A diagnosis is obtained within 20 minutes. Patient is kept under general anesthesia. If the result is positive, the surgeon proceeds with radical surgery. Consent for mastectomy should be obtained preoperatively. 3. **True-cut biopsy:** done under local anesthesia with a special needle that cuts a core of tumor tissue. 4. **Fine needle aspiration cytology (FNAC):** It depends on examination of cells to detect criteria of malignancy in them-The aspiration can be done in the outpatient clinic using fine needle. A skilled cytologist is needed. * **Advantages of FNAC:** 1. Very simple, inexpensive and accurate procedure. 2. Give a definite diagnosis in 90% of cases. 5. **Biopsy from impalpable breast masses:** the radiologist can place a wire inside the lesion under mammographic guidance. At operation, the mass is removed with the wire for histological assessment. ### **[F] Aspiration of a cyst:** * A breast cyst is considered benign if: 1. The fluid is not blood stained. 2. The cyst disappears completely with aspiration. 3. Does not recur within 2 weeks. 4. In case of doubt, the fluid is subjected to cytological examination. ### **[G] Investigations to detect distant metastasis: routinely done by:** 1. Chest x-ray. 2. Ultrasound examination of the pelvis and abdomen 3. Alkaline phosphatase (a high level indicates bone or liver deposits) 4. Further tests (needed in special situations): - *(a) Bony pains require x-rays and isotope bone scan.* - *(b) Suspicion of cerebral secondaries is an indication for CT examination.* - *(c) PET (positron emission tomography) scan.* ## Triple assessment: It means comparing the results of 1) Clinical examination 2) Mammography or ultrasonography 3) FNAC If the three parameters are concordant, the surgeon can rely on the diagnosis. ## Early detection 1. **Breast self-examination:** All women over age of 20 years should be advised to examine their breasts monthly, one week after the menstrual period. The physician instructs the woman as how to conduct a systematic inspection and palpation. 2. **Screening programs:** In some Western countries, high-risk women are subjected to regular clinical examination and mammography, every one or three years. ## Treatment ### **I. Early (potentially curable) breast cancer** This is defined as stages I and II in UICC staging. ### **[A] Surgery:** Different surgical options are available (all of them give almost equal results): ### **[1] Conservative therapy:** It includes: 1. **Local wide excision with a 2cm safety margin.** If the lesion is close to skin, part of it may be excised. 2. **The sentinel lymph node:** is the first node in the axilla to be affected. injection of patent blue violet or a radioactive sulphur colloid near the tumor will allow Identification, excision and immediate pathological examination of the sentinel node - If the node is positive for metastasis: axillary clearance is done. - If the node is negative for metastasis: no further excision of lymph nodes. 3. **Postoperative radiotherapy for 4 weeks directed to the breast.** **Advantages:** 1. If done for the properly indicated patients, the operation provides good results that are equal to radical mastectomy. 2. The breast is preserved minimizing psychological trauma. **Indications:** 1. Small tumor ≤ 4cm. 2. Sometimes, large lesions (up to 5 cm) in large breasts. 3. Peripheral lesions. **Contraindications:** 1. Pregnancy. 2. Large or central tumors in small breasts (no cosmetic advantages). 3. Multicentric disease as detected by soft tissue mammography. 4. Collagen vascular disease (poor tolerance to radiotherapy). 5. In situ breast cancer more than 20% due to the common incidence of multicentricity. ### **[2] Modified radical mastectomy (of Patey):** - It involves removal of the following structures in one block: - Skin ellipse over the tumor with at least 5 cm safety margin including the areola and nipple. - The whole breast including the tumor. - The pectoralis minor muscle is either removed or its tendon is cut to open the axilla. - All axillary lymph nodes and axillary fat medial to the axillary vein. NB. Axillary vessels, axillary nerve, nerve to serratus ant. and nerve to latissimus dorsi are spared After Patey's mastectomy radiotherapy is advised for patients with: 1. Positive axillary lymph nodes. 2. Tumors in the medial half of the breast. ### **[B] Adjuvant chemotherapy and hormonal treatment:** 1. **Hormonal therapy:** For all hormone receptor positive cases. It reduces ipsilateral and contralateral breast recurrence by 40%.tamoxifen blocks estrogen receptors and anastrazole is an aromatase inhibitor which inhibits peripheral conversion of androgen to estrogen. 2. **Chemotherapy:** is indicated for: 1. Positive axillary nodes. 2. All patients below 70 years. 3. Tumors more than 1 cm. 4. Hormone receptor negative and Her2/neu positive tumors (denote aggressive tumors). 3. **Targeted therapy:** for Her2/neu positive tumors. Monoclonal antibodies are given against Her2/neu receptors (herceptin). ### **[C] Follow up:** - After treatment, patients are reviewed at regular intervals, usually 3 months for the first 2 years, 4 monthly for the next 3 years, and annually thereafter. This is required to: 1. **Detect and treat complications of mastectomy:** - *(A) Psychiatric morbidity:* caused by loss of the breast. - *(B) Arm edema results from:* - Excision of lymphatics. - Lymphatic obstruction by radiotherapy. - Lymphangitis caused by infection. - Malignant axillary recurrence blocking them. - Thrombosis of the axillary vein. **How to avoid?** - *Avoidance of radiotherapy to the axilla, which has been surgically evacuated of its nodes, reduces the possibility of lymphatic edema.* - *The patient is warned to avoid minor trauma to the ipsilateral hand & should wear gloves when carrying out rough work in order to avoid infection & lymphangitis.* **Treatment:** (difficult) Arm elevation, massage & elastic or pneumatic arm compression are partially effective. N.B1: brawny edema: hard but still pitting edema due to Infiltration of lymph vessels. N.B2: elephantiasis surgica: lymphedema secondary to block dissection of lymph nodes. N.B3: stewart-treves disease: It is lymphanglosarcoma on top of long-standing lymphedema. 2. **Detect local recurrence or distant disease.** 3. **To do annual mammography of the contralateral breast.** 4. **Ladies who are free of the disease after two years can be considered for reconstruction of breast using either a synthetic implant or a myocutaneous flap (e.g. Transverse Rectus Abdominus Myo-cutaneous flap TRAM).** Some surgeons prefer immediate reconstruction for low risk patients. 5. **Patients are instructed:** Not to get pregnant for at least three years & to use non-hormonal contraception. ## II. Treatment of Intermediate disease (locally advanced breast cancer) - It includes tumors larger than 5 cm or fixed axillary or internal mammary nodes. - Distant metastasis should be excluded. - **Treatment:** Neoadjuvant (pre-operative) chemotherapy with the aim of down staging of the tumor. Then either conservative surgery or modified radical mastectomy is done according to the response to treatment. ## III. Advanced (incurable) breast cancer - It includes stages III and IV in UICC staging - Fungation, ulceration & Inflammatory carcinoma are included in this category. - **Endocrine therapy and chemotherapy are the two main lines of treatment. **Surgery and radiotherapy are of secondary value. ### **[A] Endocrine therapy:** - Patients who are more likely to respond are: 1) Postmenopausal women. 2) Estrogen receptor positive tumors. 3) Progesterone receptor positive tumors. - **The methods in common use are:** 1. **Tamoxifen (Nolvadex tablets):** the first line hormone therapy. It is an antiestrogen that blocks estrogen receptors preventing the hormone from activating cancer cells. The dose is 10 mg twice daily. It is not given for more than 5 years to avoid risk of endometrial cancer or thrombogenecity. 2. **Aromatase inhibitors.** 3. **Raloxifen:** as tamoxifen with less side effects. ### **[B] Chemotherapy:** It is indicated for the following cases: 1) Rapidly progressive disease. 2) Premenopausal women. 3) Receptor negative cases. 4) Hormone failure. 5) Liver metastases. Combinations commonly used include: Cyclophosphamide, Methotrexate and 5-Flurouracil (CMF). N.B: it can be used as a targeted therapy for Her2/neu positive cases. ### **[C] Radiotherapy:** It is indicated for the following cases: 1. Pain whether due to bone or soft tissue involvement. 2. To control tumor fungation. ### **[D] Surgery:** It is indicated for the following cases: - Radical mastectomy may be done for advanced local disease (stage III). It provides good local control. - Simple mastectomy to remove fungating tumor. ### **[E] Management of specific problems:** 1. **Pleural effusion:** Commonly responds to systemic therapy and chest tube drainage. If not, local instillation of the cytotoxic bleomycin through the tube may be required. 2. **Pathological fractures:** - Internal fixation is used. The patient is given radiotherapy to the fracture site. 3. **Spinal cord compression:** requires urgent surgical cord decompression, with stabilization followed by radiotherapy. 4. **Cerebral metastases:** are treated by a combination of corticosteroids and radiotherapy. Occasionally a solitary brain metastasis is suitable for surgical excision. The requirements are: - *(a) Well-controlled breast primary.* - *(b) A long life expectancy.* - *(c) An accessible area in the brain.* 5. **Liver metastases:** Chemotherapy. ### **6. Hypercalcemia:** Treatment: Is correction of dehydration by IV fluids + frusemide + prednisolone. ### **7. Superior vena caval obstruction:** Requires urgent radiotherapy. ## Prognosis: Prognosis of patients with breast carcinoma depends on the following factors: 1. **The type of the tumor:** The best prognosis is provided by the in situ carcinoma and Paget's disease, while the worst is the Inflammatory carcinoma. 2. **The T stage of the primary tumor:** The higher the T stage, the worse is the prognosis. 3. **The site of the tumor:** Medial half tumors have a worse prognosis than those of lateral half due to early involvement of the internal mammary lymph nodes. 4. **The involved lymph nodes:** Size, mobility, number and location of the involved lymph nodes. Assessment of lymph node involvement depends on the histological examination: -(a) Large fixed nodes are of bad prognosis. -(b) The number of involved nodes largely affects the prognosis: - *Patients with negative axillary nodes have a 10-year survival rate of 65%* - *Patients with 1- 3 positive axillary nodes have a 10-year survival rate of 38%* - *Patients with more than 4 positive axillary nodes have a 10-year survival rate of 13%* -(c) The prognosis worsens the higher the level of the affected nodes in the axilla. High-level nodes carry a bad prognosis. 5. **The presence of distant metastasis** 6. **Hormone receptor status:** Receptor positive tumors respond more often to hormonal therapy and have a better prognosis than those that are receptor negative. ## Investigations of clinically doubtful breast mass | | Mammography | Fine needle aspiration | | |---|---|---|---| | | Fluid (cyst) | No fluid (solid) | | | | Doubtful malignancy | Definitively benign | Reassure | |   |   | Manage according to cause |   | | | | | Cytology | |---|---|---|---| | | | | - ve | | | | | + ve | | | •No blood | •Blood stained | | | | •Mass disappears | •Residual mass | | | | •No recurrence | | | | | •Negative cytology | | | | | Benign cyst | | | | | | | | | | | | | |---|---|---|---| | | | Reassure | Excision or True cut biopsy | | | | | | | | | Benign | Malignant | | | | | | | | | | | |---|---|---|---| | | | | | | | | | | | | | | | | | | Reassure & manage | Early | Advanced | | | | | Staging | | | | | CXR, LFTS | | | | | Abd U/S (or CT) |