What is Breast Cancer

Ductal Carcinoma of the Breast is one of the main types of breast cancer. The breast is an organ designed to manufacture and deliver milk to the infant. The majority of the breast is composed of fatty tissue. Milk glands lie within this fatty tissue and are connected to the nipple via a series of ducts. The breast is also rich in blood vessels and lymphatic channels.

There are various types of breast cancer categorised by the way the cells appear under the microscope. The main types are:
* Ductal carcinoma (70-80%): cancer cells that resemble the ducts of the breast
* Lobular carcinoma (5-10%): cancer cells that resemble the lobules or glands of the breast
* Medullary carcinoma (1 to 5%)
* Mucinous (1 to 6%)
* Tubular carcinoma (2%)

The types of breast cancer vary in their prognosis and the way in which they present. Ductal carcinoma (in situ and invasive) will be discussed here. The term ‘in situ’ refers to pre-invasive breast cancer. This is breast cancer which has not yet penetrated (’invaded’) through the basement membrane (the membrane at the base of the epithelial lining of ducts or glands). In situ carcinoma has the potential to become invasive carcinoma, and so is treated as an early form of breast cancer. In the left-hand image below, you can see how the normal cells which line the ducts of the breast might look. In ductal carcinoma in situ (DCIS, the image to the right), the duct cells have developed the ability to multiply out of control - one of the characteristics of cancer. The cancerous cells are filling the duct, but have not yet spread beyond the lining of the duct. This is known as DCIS.

The next set of images below show the cells of invasive breast cancer. These cells have not only multiplied out of control, filling the duct, but have also developed the ability to spread, or invade, beyond the lining of the ducts. This is invasive ductal carcinoma, or IDC.

Who gets Breast Cancer?

Breast cancer is common. Breast cancer is one of the top two causes of cancer deaths together with lung cancer in most developed countries. 99% of breast cancers occur in women with 1% in men. Incidence increases with age. Breast cancer is rare in those under the age of 30, but presents in up to 1 in 14 women over the age of 70. 15-30% of breast cancers are of the in situ type whilst 70-85% are of the invasive type. Ductal carcinoma is the most common making up 80% of all breast cancers. DCIS has increased in incidence since the introduction of mammographic screening. It is now seen in 20-25% of women over 50 screened with mammography. Geographically, breast cancer is found worldwide.

Predisposing Factors

The main risk factors for breast cancer are:

* Increasing age
* A family history of breast cancer
* Proliferative breast disease
* Hormonal factors: women who begin menstruation early, women who have a late menopause, late or few pregnancies, or who are obese. Some evidence is emerging that long term oestrogen therapy (for example, long-term use of the oral contraceptive pill, or hormone replacement therapy (HRT)) may increase risk, as may a diet which is high in fat.
* Others: exposure to radiation; geographical factors.

Progression

Ductal carcinoma in situ (DCIS) is an ‘early’ form of breast cancer. In this case, cells lining the ducts of the breast have become abnormal and are growing more rapidly than usual, but are not able to spread beyond the ducts. Women with DCIS are at higher risk of developing invasive ductal carcinoma. Invasive ductal carcinoma has developed the ability to spread beyond the ducts of the breast. Ductal carcinoma of the breast spreads initially by direct invasion of overlying skin and adjacent fat. Spread into lymphatics and to lymph nodes in the axilla is the most important step, since from there it can spread to lymph nodes in the neck and supraclavicular region and into blood vessels. Once in the blood vessels, spread is possible to distant organs such as the bones, lung or liver.

Probable Outcomes

Early breast cancer has a good (greater than 80%) 5 year survival. Important prognostic factors which can help predict survival include involvement of lymph nodes, the size of the tumour, and how aggressive the tumour cells are. If the cancer has metastasised (spread) to lung, liver or bone at diagnosis, 5-year survival rates are significantly lower. As mentioned above, women with DCIS are at increased risk of developing invasive breast cancer in the future. However, as most cases of DCIS are now treated, it is not known exactly how high this risk is, or how quickly the progression from in situ to invasive cancer is likely to occur.

How is Breast Cancer Diagnosed?

Any breast symptom, such as a lump or nipple discharge, is assessed with the ‘triple test’. This includes examination of the breast, imaging of the breast through mammography or ultrasound, and sampling of the breast tissue with fine needle aspiration (FNA), core biopsy or open biopsy. Following a diagnosis of breast cancer, blood tests including Full Blood Count and Liver Function Tests may be used to assess the possibility that the cancer may have spread to the liver or bone marrow. Other imaging tests, including chest x-rays, bone scan, abdominal CT or liver ultrasound may also be used if symptoms suggest that the cancer has spread.

How is Breast Cancer treated?

Surgical treatment of breast cancer aims to achieve total disease control through removal of the primary breast tumour, along with any local extension.
Virtual Medical Centre Video

Surgical treatment can be divided into two major streams:

* Breast conserving surgery with complete local excision (CLE) and axillary dissection, or
* Total mastecomy with axillary dissection.

These two procedures are considered similar in terms of 5- and 10-year survival rates. The decision as to which procedure is more appropriate is therefore based on clinical features, such as the size and location of the tumour, and patient preference.

* Larger, widespread cancers or cancer near the nipple may usually require mastectomy (removal of the whole breast). This can be followed by reconstructive surgery.
* Smaller tumours, or tumours located in the outer quadrant in larger breasts may be removed by lumpectomy or partial mastectomy. Radiotherapy usually follows the procedure.
* Axillary dissection refers to the removal of lymph nodes in the axilla (armpit). These lymph nodes are commonly the first site of metastasis (spread) of a breast tumour, and axillary dissection is routinely done to ensure all cancer cells are removed. Rarely, with some very small and well-defined cancers, axillary dissection may not be necessary.

Adjuvant therapy refers to chemotherapy, radiotherapy or hormone therapy which is done with the aim of destroying any cancer cells not removed by surgery. Chemotherapy protocols include:

1. CMF:
* Cyclophosphamide 100mg/m2 PO days 1-14
* Methotrexate 40mg/m2 IV days 1+8
* 5-Fluorouracil 600mg/m2 IV days 1+8 (repeat every 4 weeks for 6 cycles)
ALL I.V. CMF:
* Cyclophosphamide 750mg/m2 IV day 1 (or 150mg/day)
* Methotrexate 60mg/m2 IV day 1
* 5-Fluorouracil 750mg/m2 IV day 1 (repeat every 3 weeks)
2. AC:
* Doxorubicin 60 mg/m2
* Cyclophosphamide 600 mg/m2
3. For High Risk Patients:
* TAC
* FEC 75
* FEC 100
* Docetaxel
* Paclitaxel
Modifications:
1. Post menopausal:
* Tamoxifen 20 mg PO daily
2. Locally Advanced FAC:
* 5-Fluorouracil 600 mg/m2 IV day 1 + 8
* Doxorubicin 60mg/m2 IV day 1 (vesicant)
* Cyclophosphamide 600mg/m2 IV day 1 (repeat every 4 weeks)
4. Stage IV: First line chemotherapy:
* CMFP (oral or IV) (add prednisolone 40mg/m2 PO days 1-14 to CMF)
Reassess every 3 courses Treat until maximum response
* Trastuzumab (Herceptin) and Taxanes
* Herceptin 4 mg/kg IV over 90 minutes then 2mg/kg/week over 30 minutes until progression
o WITH Docetaxel 75 mg/m2 IV over 1 hour every 3 weeks for 6 cycles OR
o Paclitaxel 90 mg/m2 IV over 60 minutes weekly
5. Herceptin single agent:
* Herceptin 4 mg/kg IV over 90 minutes then 2mg/kg/week over 30 minutes until progression
6. Second line chemotherapy:
* Doxorubicin 60mg/m2 IV day 1 (vesicant) (repeat every 3 weeks)
7. Third line chemotherapy:
* Docetaxel 75 mg/m2/day over 1 hour as starting dose can escalate to 100mg.m2/day IV over 1 hour. In heavily pretreated patients or those with poor liver function can start at 60 mg/m2. (repeat every 3 weeks)
* Docetaxel (weekly) 36 mg/m2/week over 1 hour for 6 weeks then 2 weeks off
* Paclitaxel 175mg/m2/day over 3 hours IV (repeat every 3 weeks)
* Paclitaxel (weekly) 100 mg/m2 IV over 1 hour
8. Fourth line chemotherapy:
* Capecitabine 2500 mg/m2 divided into 2 doses daily po 2 weeks every 3 weeks
* Mitomycin C 10 mg/m2 IV Day 1 (vesicant)
* Vinblastine 5 mg/m2 IV Day 1 and 15 (vesicant) (repeat every 4 weeks)
9. Hormonal Therapy:
* Tamoxifen 20 mg. po daily or Anastrozole 1mg po daily
* Then Medroxyprogesterone acetate 500 mg po daily Or Exemestane 25 mg/day
10. Premenopausal Advanced Breast Cancer:
* Zoladex 3.6 mg SC every month
* Tamoxifen 20 mg/day
11. Bone metastases: When the tumour has spread to bone, zoledronic acid can be used to help prevent fractures.
* Zoledronic acid 4mg iv over 15mins every 28 days
12. Breast Cancer (Bone Predominant):
* Pamidronate 90mg IV over 2 hours.

If the tumour has spread to bone, treatment with zoledronic acid can help prevent tumour growth in bone and subsequent bone fractures. Symptoms that may require attention include bone pain from bone metastases, visceral (organ) pain from liver or lung metastases and neurogenic (nerve) pain if nerve tissue is compressed. Improvement in symptoms is an important measurement. Hormone therapies: Women with hormone receptor-positive tumours (eg. oestrogen-receptor positive tumours) should be offered adjuvant hormone therapies such as tamoxifen or ovarian ablation therapy. Click the links below to see for information on other breast cancers:

* Breast cancer - Adenocarcinoma of the breast
* Breast pain
* Male breast cancer
* Breast cancer - Lobular carcinoma of the breast
* Inflammatory breast cancer

Breast Cancer References

1. Australian Institute of Health and Welfare & National Breast Cancer Centre 2006. Breast cancer in Australia: an overview, 2006. Cancer series no. 34. cat. no. CAN 29. Canberra: AIHW.
2. Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison’s Principles of Internal Medicine. 16th Edition. McGraw-Hill. 2001
3. Cotran RS, Kumar V, Collins T. Robbins Pathological Basis of Disease Sixth Ed. WB Saunders Company 1999.
4. Dr Guy Van Hazel, Oncologist, Mount Hospital, Perth
5. Kumar P, Clark M. Clinical Medicine. Fourth Edition. WB Saunders, 1998.
6. National Breast Cancer Centre. 2003. ‘The clinical management of ductal carcinoma in situ, lobular carcinoma in situ and atypical hyperplasia of the breast,’ First Edition. National Breast Cancer Centre, Camperdown,NSW. [online] Available from: http://www.nbcc.org.au/bestpractice/resources/CMW_dcisbook.pdf
7. National Breast Cancer Centre. 2001. ‘Clinical practice guidelines for the management of early breast cancer:Second edition’. National Breast Cancer Centre, Camperdown,NSW. [online] Available from: http://www.nhmrc.gov.au/publications/synopses/cp74syn.htm
8. Schwartz, GF, Solin, LJ, Olivotto, IA, et al. Consensus Conference on the Treatment of In Situ Ductal Carcinoma of the Breast, April 22-25, 1999. Cancer 2000; 88:946.
9. Talley NJ, O’Connor Simon. Clinical Examination. Fourth Edition. MacLennan & Petty, 2001

Related Documents:

* For a PPT presentation titled ‘NCCTG N9831: Whether Trastuzumab adds to the benefit of adjuvant paclitaxel in resected HER-2 positive breast cancer’ please click here.
* For a PPT presentation titled ‘The Role of Bevacizumab in the Treatment of Metastatic Breast Cancer’ please click here.
* For a PPT presentation titled ‘A Randomized Phase III Trial of Paclitaxel versus Paclitaxel plus Bevacizumab as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer’ please click here.
* For a PPT presentation titled ‘Doxorubicin and Cyclophosphamide Followed by Paclitaxel with or without Trastuzumab as Adjuvant Therapy for Patients with Her-2 Positive Operable Breast Cancer’ please click here.
* For a PPT presentation titled ‘Targeting HER-2 in the Adjuvant Setting’ please click here.
* To view these PPT slides with a free PowerPoint viewer 2003, please click here.

Regimens Used in the Treatment of This Disease:

* 5-Fluorouracil
* AC (Doxorubicin + Cyclophosphamide)
* ACE (Doxorubicin + Cyclophosphamide + Etoposide)
* Capecitabine + Docetaxel
* Capecitabine + Paclitaxel
* CMF (Cyclophosphamide + Methotrexate + 5-Fluorouracil)
* Docetaxel
* Doxorubicin
* Doxorubicin (Liposomal)
* EC (Epirubicin + Cyclophosphamide)
* Epirubicin
* FEC 100 (5-Fluorouracil + Epirubicin + Cyclophosphamide)
* FEC 75 (5-Fluorouracil + Epirubicin + Cyclophosphamide)
* Gemcitabine + Paclitaxel
* Mitomycin
* Mitozantrone
* Paclitaxel + Trastuzumab
* TAC (Docetaxel + doxorubicin + cyclophosphamide)

Treatments Used in This Disease:

* Breast Conserving Surgery
* Mastectomy

Drugs/Products Used in the Treatment of This Disease:

* Methotrexate Injection BP
(Methotrexate)

* Arimidex
(Anastrozole)

* Aromasin
(Exemestane)

* Avastin
(Bevacizumab)

* Femara
(Letrozole)

* Gemzar
(Gemcitabine hydrochloride)

* Haldol Decanoate
(Haloperidol decanoate)

* Herceptin
(Trastuzumab)

* Megace
(Megestrol acetate)

* Onkotrone
(Mitozantrone hydrochloride)

* Pamisol
(Disodium pamidronate)

* Provera
(Medroxyprogesterone acetate)

* Tamoxifen-BC
(Tamoxifen citrate)

* Taxotere
(Docetaxel)

* Tykerb
(Lapatinib Ditosylate)

* Xeloda
(Capecitabine)

* Zoladex 3.6mg and 10.8 mg Implant
(Goserelin acetate)

* Zometa
(Zoledronic acid)

Tykerb is the brand name for a new anti-cancer medication called lapatinib. Tykerb works by inhibiting kinase proteins in cells which interferes with the growth of cancer cells. Tykerb is used in combination with another anti-cancer drug called capecitabine (Xeloda), for the treatment of advanced breast cancer that is positive for the HER2 protein.