Breast cancer

Breast cancer

Globally, breast cancer is the most frequently diagnosed lifethreatening
cancer in women and is the leading cause of cancer death among women. Breast cancer can be discovered while in situ (localized) or as a malignant neoplasm (spreading).

The female breasts
An adult woman’s breasts are milk?producing glands on the front of the chest wall, resting on the pectoralis major, supported by and attached to the front of the chest wall on either side of the sternum by ligaments. There are 15–20 lobes arranged in a circular fashion in each breast. Each lobe comprises many lobules, with glands that produce milk in response to hormones. A number of early breast carcinomas are asymptomatic, particularly if they are discovered during a breast?screening programme. Larger tumours can present as a painless mass. Pain or discomfort is not usually a symptom of breast cancer. A large number of breast cancer cases in the UK can be explained by factors that influence exposure to oestrogen, including reproductive and hormonal factors, obesity, alcohol and physical activity. Breast cancers are predominantly linked to modifiable lifestyle and environmental factors.

Pathophysiology
The majority of breast cancers arise from either the epithelial lining of ducts, known as ductal, or from the epithelium of the terminal ducts of the lobules and these are called lobular. Carcinoma can be invasive or in situ. Most cancers arise from intermediate ducts and are invasive. They eventually grow through the wall of the duct and into the fatty tissue. Current understanding of breast cancer is that invasive cancers arise through a series of molecular alterations at the cell level. These alterations result in breast epithelial cells with remarkable features and uncontrolled growth. An infiltrating carcinoma of the nipple epithelium, called Paget’s disease of the breast, accounts for approximately 1% of all breast cancers. Inflammatory carcinoma exists in less than 3% of all cases; there is a rapidly growing, sometimes painful mass increasing the breast and causing the skin covering it to become red and warm. There may be widespread infiltration of tumour. Staging of the tumour Tumour size, lymph node status and distant metastasis are taken into account when staging the tumour. The various tests and investigations required to make a diagnosis can also give some information about the stage. Understanding the stage is important as this helps the clinician to decide on the most appropriate treatment.

Signs and symptoms
Most early breast carcinomas are asymptomatic, especially if discovered during a breast?screening programme. Larger tumours may present as a painless mass. Pain (mastalgia) or discomfort is not usually a symptom of breast cancer; only 5% of women with a malignant mass have breast pain.
Most women will have felt a lump, there may be nipple change and in some cases nipple discharge; skin contour changes can occur. Intraduct carcinoma can present as a bloody discharge from the nipple.

Investigations
A variety of investigations are used; however, evaluation starts with an ordered inquiry that begins with symptoms and a general clinical history, along with a physical examination of the breasts, the axillary and cervical lymph nodes. Once the examination has been concluded other investigations may be required; these are used to make a diagnosis and to help with staging. Investigations should be aligned to local national guidance. Triple assessment includes the following components, clinical examination, imaging (including mammography, ultrasonography or both) and needle biopsy. Mammography is more appropriate for less dense breasts and is almost always undertaken; ultrasound and mammography can detect more invasive tumours. Ultrasound is effective particularly when breast tissue is dense; in the younger woman it can be diagnostically more useful than mammography. MRI is used in women with dense breast tissue, cases of familial breast cancer associated with BRCA mutations, silicone gel implants, positive axillary lymph node status with occult primary tumour in the breast or if multiple tumour foci are suspected. Core needle biopsy (image?guided) should be obtained before any surgery. Ultrasound or stereotactic mammographic guidance can be used. Open biopsy (needle localization), radio?opaque needles are used to guide biopsy (this can be done under local anaesthetic). Where there are palpable lesions fine?needle aspiration is required. Core needle biopsy is usually used for larger lesions. Excision biopsy (under local anaesthesia) allows the entire lesion to be removed). Incisional biopsy provides for part of a lesion to be removed (lesions 4â•›cm or larger).
Specific staging investigations include routine blood tests, such as liver function tests, chest X?ray; if metastases are suspected a CT scan is needed. Bone scintigraphy is required if there are distant metastases. Positron emission tomography can detect distant metastases.

Management
Treatment must be patient?centred, acknowledging the woman’s individual needs and preferences. Discussion and involvement of the woman’s family should, with their consent, be enabled. Prognosis of patients with breast cancer depends on biological characteristics of the cancer, the patient and on appropriate therapy. The primary treatment for early stage breast cancer is surgery; many women are cured with surgery alone. The aim of breast cancer surgery includes complete resection of the primary tumour with negative margins, reducing the risk of local recurrences, and pathological staging of the tumour and axillary lymph nodes providing necessary prognostic information. Adjuvant treatment of breast cancer is intended to treat micrometastatic disease (breast cancer cells escaping into the breast and regional lymph nodes but which have not yet had an established identifiable metastasis). Adjuvant treatment involves radiation therapy and a number of chemotherapeutic and biological agents. Treatment attempts to reduce the risk of future recurrence, and in so doing reduce breast cancer?related morbidity and mortality.












Cervical cancer
Cancer of the cervix is one of the few preventable cancers; it is the most common cancer in women under 35 years old. Globally, cervical cancer is the second most common female malignancy. It has been demonstrated that cervical screening programmes are associated with improved rate of cure of cervical cancer. There are several risk factors associated with cervical cancer. The presence of the human papilloma virus (HPV) (highest risks are HPV types 16 and 18), women of low socioeconomic status, multiparous, those engaging in sexual activity at a young age or with multiple partners and cigarette smoking, all increase the risk. Women with a history of sexually transmitted infections, especially herpes or genital warts, and who do not attend cervical screening are also at greater risk. Those women who are immunosuppressed have a higher risk of cervical carcinoma.

Pathophysiology
There are three types of cervical cancer:
•â•¢ Squamous cell cervical cancer is the most common
•â•¢ Adenocarcinoma cervical cancer is less common
•â•¢ Mixed cell
All are diagnosed and treated in a similar way and all three cause both pre?invasive and invasive disease. HPV is seen as the vector that confers susceptibility to neoplastic conversion or directly incites transmutation to a malignant phenotype in some infected epithelial cells. Neoplastic transformation usually originates at the squamocolumnar junction of the cervix. Varying degrees of cervical intra?epithelial neoplasia (CIN) exist; these are graded from 1 to 3 on the basis of increasing severity of the lesion. Carcinoma in situ exists when all epithelial layers consist of neoplastic cells. It usually takes 10–20 years for intra?epithelial neoplasia to progress to invasive disease. Histologically many tumours exhibit squamous histology. Invasive cancer breaches the epithelial basement membrane at any point.
Cervical smears may be particularly effective in detecting preinvasive or early?stage disease as women with early invasive cervix cancer may have a cervix that appears normal to the naked eye. The majority of these women are asymptomatic; however, with advanced cancer women often experience symptoms. Invasive cancers display two chief modes of extension: local spread and metastasis via lymphatic system and bloodstream. Cervical cancer can have an ulcerative or exophytic appearance. Local expansion usually involves extension to the endocervix or vaginal fornices, followed by progressive infiltration of parametrial tissues, uterine corpus, bladder or rectum. Lymphatic dissemination usually occurs in a stepwise progression. Pelvic nodes become involved; spread via the bloodstream may give rise to distant implants of cancer in lungs, bones, liver or other tissue. The likelihood of metastasis grows with expanding size and expanse of tumour.

Signs and symptoms
Screening detects a substantial number of cases. The first symptoms of established cervical carcinoma include vaginal discharge, varying in amount, which is either intermittent or continuous. In the early stages bleeding can be spontaneous, but can occur after sex, micturition or defaecation. Women may ignore this if it is scanty and attribute this to normal menstrual dysfunction. On occasion, severe vaginal bleeding may require emergency hospital admission. There may be vaginal discomfort and urinary symptoms.
Late symptoms can include painless haematuria, chronic urinary frequency, painless fresh rectal bleeding, altered bowel habit, leg oedema, pain and hydronephrosis, leading to renal failure that may indicate late signs of pelvic wall involvement. In more advanced disease, women develop pelvic discomfort or poorly localized pain described as dull or boring in the suprapubic or sacral regions; this can be persistent or intermittent. Examination can be relatively normal in early stage cancer.
On the cervix there may be white or red patches. With progression of the disease this can lead to an abnormal appearance of the cervix and vagina, as a result of erosion, ulcer or tumour. There may be a mass or bleeding on rectal examination as a result of erosion. A pelvic bulkiness/mass may be present when bimanual palpation is undertaken, due to pelvic spread. Lymphatic or vascular obstruction can cause the development of leg oedema. With the presence of liver metastases there may be hepatomegaly. Pleural effusion or bronchial obstruction indicates pulmonary metastases.

Investigations
If cervical cancer is suspected, a number of investigations and tests are required to confirm diagnosis and to stage the disease. The following investigations may be undertaken. A colposcope is used to show the cervix in detail, acting as a magnifying glass to identify abnormal cervical cells. A biopsy is taken from the cervix and histologically examined. Large loop excision of the transformation zone (LLETZ) is used when the colposcope fails to identify any abnormality. Local anaesthesia is used and a thin wire, which is shaped in a loop, is then used to cut away the affected area. Needle excision of the transformation zone (NETZ) is similar to LLETZ. The thin wire used to cut away the affected area is straight, as opposed to a loop, acting like a knife permitting the precise area of affected tissue to excised. Cone biopsy, used when the abnormal area in the cervix cannot be seen with a colposcope, is usually conducted under a general anaesthetic, although local anaesthetic can be used.
Other investigations include full blood count, renal and liver function tests, chest X?ray, intravenous urogram, CT scan, barium enema or proctoscopy (to assess rectal involvement), cystoscopy (assesses bladder invasion) and MRI scan.

Management
The treatment of cancer of the cervix will depend on the stage. There are several approaches to treatment, for example surgery, radiotherapy, pharmacotherapy chemotherapy or a combination of these treatments. The extent of surgery will be dictated by the tumour stage, the age of the patient as well as any comorbidities. Normally, a combination of external beam therapy and intra?cavity brachytherapy is used.